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    Author Title Year Journal/Proceedings DOI/URL
    Alho, J., Green, B.M., May, P.J.C., Sams, M., Tiitinen, H., Rauschecker, J.P. & Jääskeläinen, I.P. Early-latency categorical speech sound representations in the left inferior frontal gyrus. 2016 Neuroimage
    Vol. 129, pp. 214-223School: Brain and Mind Laboratory, Department of Neuroscience and Biomedical Engineering (NBE), School of Science, Aalto University, 00076, AALTO, Espoo, Finland; MEG Core, Aalto NeuroImaging, Aalto University, 00076, AALTO, Espoo, Finland; AMI Centre, Aalto NeuroImaging, Aalto University, 00076, AALTO, Espoo, Finland. Electronic address: iiro.jaaskelainen@aalto.fi. 
    DOI URL 
    Abstract: Efficient speech perception requires the mapping of highly variable acoustic signals to distinct phonetic categories. How the brain overcomes this many-to-one mapping problem has remained unresolved. To infer the cortical location, latency, and dependency on attention of categorical speech sound representations in the human brain, we measured stimulus-specific adaptation of neuromagnetic responses to sounds from a phonetic continuum. The participants attended to the sounds while performing a non-phonetic listening task and, in a separate recording condition, ignored the sounds while watching a silent film. Neural adaptation indicative of phoneme category selectivity was found only during the attentive condition in the pars opercularis (POp) of the left inferior frontal gyrus, where the degree of selectivity correlated with the ability of the participants to categorize the phonetic stimuli. Importantly, these category-specific representations were activated at an early latency of 115-140ms, which is compatible with the speed of perceptual phonetic categorization. Further, concurrent functional connectivity was observed between POp and posterior auditory cortical areas. These novel findings suggest that when humans attend to speech, the left POp mediates phonetic categorization through integration of auditory and motor information via the dorsal auditory stream.
    BibTeX:
    @article{AlhoGreenMayEtAl2016,
      author = {Alho, Jussi and Green, Brannon M. and May, Patrick J C. and Sams, Mikko and Tiitinen, Hannu and Rauschecker, Josef P. and Jääskeläinen, Iiro P.},
      title = {Early-latency categorical speech sound representations in the left inferior frontal gyrus.},
      journal = {Neuroimage},
      school = {Brain and Mind Laboratory, Department of Neuroscience and Biomedical Engineering (NBE), School of Science, Aalto University, 00076, AALTO, Espoo, Finland; MEG Core, Aalto NeuroImaging, Aalto University, 00076, AALTO, Espoo, Finland; AMI Centre, Aalto NeuroImaging, Aalto University, 00076, AALTO, Espoo, Finland. Electronic address: iiro.jaaskelainen@aalto.fi.},
      year = {2016},
      volume = {129},
      pages = {214--223},
      url = {http://dx.doi.org/10.1016/j.neuroimage.2016.01.016},
      doi = {http://doi.org/10.1016/j.neuroimage.2016.01.016}
    }
    
    Avdoshina, V., Fields, J.A., Castellano, P., Dedoni, S., Palchik, G., Trejo, M., Adame, A., Rockenstein, E., Eugenin, E., Masliah, E. & Mocchetti, I. The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons. 2016 Neurotox Res
    Vol. 29(4), pp. 583-593School: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. moccheti@georgetown.edu. 
    DOI URL 
    Abstract: Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated neurotoxicity remain unclear, thus precluding an effective treatment of the neurological complications. The present study was undertaken to characterize novel mechanisms of HIV neurotoxicity that may explain how HIV subjects develop neuronal degeneration. Several neurodegenerative disorders are characterized by mitochondrial dysfunction; therefore, we hypothesized that HIV promotes mitochondrial damage. We first analyzed brains from HIV encephalitis (HIVE) by electron microscopy. Several sections of HIVE subjects contained enlarged and damaged mitochondria compared to brains from HIV subjects with no neurological complications. Similar pathologies were observed in mice overexpressing the HIV protein gp120, suggesting that this viral protein may be responsible for mitochondrial pathology found in HIVE. To gain more information about the cellular mechanisms of gp120 neurotoxicity, we exposed rat cortical neurons to gp120 and we determined cellular oxygen consumption rate, mitochondrial distribution, and trafficking. Our data show that gp120 evokes impairment in mitochondrial function and distribution. These data suggest that one of the mechanisms of HIV neurotoxicity includes altered mitochondrial dynamics in neurons.
    BibTeX:
    @article{AvdoshinaFieldsCastellanoEtAl2016,
      author = {Avdoshina, Valeria and Fields, Jerel Adam and Castellano, Paul and Dedoni, Simona and Palchik, Guillermo and Trejo, Margarita and Adame, Anthony and Rockenstein, Edward and Eugenin, Eliseo and Masliah, Eliezer and Mocchetti, Italo},
      title = {The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons.},
      journal = {Neurotox Res},
      school = {Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. moccheti@georgetown.edu.},
      year = {2016},
      volume = {29},
      number = {4},
      pages = {583--593},
      url = {http://dx.doi.org/10.1007/s12640-016-9608-6},
      doi = {http://doi.org/10.1007/s12640-016-9608-6}
    }
    
    Avdoshina, V., Taraballi, F., Dedoni, S., Corbo, C., Paige, M., Saygide?er Kont, Y., Üren, A., Tasciotti, E. & Mocchetti, I. Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal-specific tubulin. 2016 J Neurochem
    Vol. 137(2), pp. 287-298School: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: Human immunodeficiency virus-1 (HIV) promotes synaptic simplification and neuronal apoptosis, and causes neurological impairments termed HIV-associated neurological disorders. HIV-associated neurotoxicity may be brought about by acute and chronic mechanisms that still remain to be fully characterized. The HIV envelope glycoprotein gp120 causes neuronal degeneration similar to that observed in HIV-associated neurocognitive disorders subjects. This study was undertaken to discover novel mechanisms of gp120 neurotoxicity that could explain how the envelope protein promotes neurite pruning. Gp120 has been shown to associate with various intracellular organelles as well as microtubules in neurons. We then analyzed lysates of neurons exposed to gp120 with liquid chromatography mass spectrometry for potential protein interactors. We found that one of the proteins interacting with gp120 is tubulin ?-3 (TUBB3), a major component of neuronal microtubules. We then tested the hypothesis that gp120 binds to neuronal microtubules. Using surface plasmon resonance, we confirmed that gp120 binds with high affinity to neuronal-specific TUBB3. We have also identified the binding site of gp120 to TUBB3. We then designed a small peptide (Helix-A) that displaced gp120 from binding to TUBB3. To determine whether this peptide could prevent gp120-mediated neurotoxicity, we cross-linked Helix-A to mesoporous silica nanoparticles (Helix-A nano) to enhance the intracellular delivery of the peptide. We then tested the neuroprotective property of Helix-A nano against three strains of gp120 in rat cortical neurons. Helix-A nano prevented gp120-mediated neurite simplification as well as neuronal loss. These data propose that gp120 binding to TUBB3 could be another mechanism of gp120 neurotoxicity. We propose a novel direct mechanism of human immunodeficiency virus neurotoxicity. Our data show that the viral protein gp120 binds to neuronal specific tubulin ?-3 and blocks microtubule transport. Displacing gp120 from binding to tubulin by a small peptide prevents gp120-mediated neuronal loss. Our study reveals a novel target for developing adjunct therapies against viral infection that promotes neurocognitive disorders.
    BibTeX:
    @article{AvdoshinaTaraballiDedoniEtAl2016,
      author = {Avdoshina, Valeria and Taraballi, Francesca and Dedoni, Simona and Corbo, Claudia and Paige, Mikell and Saygide?er Kont, Yasemin and Üren, Aykut and Tasciotti, Ennio and Mocchetti, Italo},
      title = {Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal-specific tubulin.},
      journal = {J Neurochem},
      school = {Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA.},
      year = {2016},
      volume = {137},
      number = {2},
      pages = {287--298},
      url = {http://dx.doi.org/10.1111/jnc.13557},
      doi = {http://doi.org/10.1111/jnc.13557}
    }
    
    Bachis, A., Forcelli, P., Masliah, E., Campbell, L. & Mocchetti, I. Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala. 2016 Brain Behav Immun
    Vol. 54, pp. 170-177School: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: moccheti@georgetown.edu. 
    DOI URL 
    Abstract: Human immunodeficiency virus type 1 (HIV) infection of the brain produces cognitive and motor disorders. In addition, HIV positive individuals exhibit behavioral alterations, such as apathy, and a decrease in spontaneity or emotional responses, typically seen in anxiety disorders. Anxiety can lead to psychological stress, which has been shown to influence HIV disease progression. These considerations underscore the importance of determining if anxiety in HIV is purely psychosocial, or if by contrast, there are the molecular cascades associated directly with HIV infection that may mediate anxiety. The present study had two goals: (1) to determine if chronic exposure to viral proteins would induce anxiety-like behavior in an animal model and (2) to determine if this exposure results in anatomical abnormalities that could explain increased anxiety. We have used gp120 transgenic mice, which display behavior and molecular deficiencies similar to HIV positive subjects with cognitive and motor impairments. In comparison to wild type mice, 6months old gp120 transgenic mice demonstrated an anxiety like behavior measured by open field, light/dark transition task, and prepulse inhibition tests. Moreover, gp120 transgenic mice have an increased number of spines in the amygdala, as well as higher levels of brain-derived neurotrophic factor and tissue plasminogen activator when compared to age-matched wild type. Our data support the hypothesis that HIV, through gp120, may cause structural changes in the amygdala that lead to maladaptive responses to anxiety.
    BibTeX:
    @article{BachisForcelliMasliahEtAl2016,
      author = {Bachis, Alessia and Forcelli, Patrick and Masliah, Eliezer and Campbell, Lee and Mocchetti, Italo},
      title = {Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala.},
      journal = {Brain Behav Immun},
      school = {Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: moccheti@georgetown.edu.},
      year = {2016},
      volume = {54},
      pages = {170--177},
      url = {http://dx.doi.org/10.1016/j.bbi.2016.01.020},
      doi = {http://doi.org/10.1016/j.bbi.2016.01.020}
    }
    
    Bachis, A., Wenzel, E., Boelk, A., Becker, J. & Mocchetti, I. The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in aging mice. 2016 Neurobiol Aging
    Vol. 46, pp. 160-168School: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: moccheti@georgetown.edu. 
    DOI URL 
    Abstract: Human immunodeficiency virus 1 and its envelope protein gp120 reduce synaptodendritic complexity. However, the mechanisms contributing to this pathological feature are still not understood. The proneurotrophin brain-derived neurotrophic factor promotes synaptic simplification through the activation of the p75 neurotrophin receptor (p75NTR). Here, we have used gp120 transgenic (gp120tg) mice to investigate whether p75NTR has a role in gp120-mediated neurotoxicity. Old (?10 months) gp120tg mice exhibited an increase in proneurotrophin brain-derived neurotrophic factor levels in the hippocampus as well as a decrease in the number of dendritic spines when compared to age-matched wild type. These effects were not observed in 3- or 6-month-old mice. To test if the reduction in spine density and morphology is caused by the activation of p75NTR, we crossed gp120tg mice with p75NTR null mice. We found that deletion of only 1 copy of the p75NTR gene in gp120tg mice is sufficient to normalize the number of hippocampal spines, strongly suggesting that the neurotoxic effect of gp120 is mediated by p75NTR. These data indicate that p75NTR antagonists could provide an adjunct therapy against synaptic simplification caused by human immunodeficiency virus 1.
    BibTeX:
    @article{BachisWenzelBoelkEtAl2016,
      author = {Bachis, Alessia and Wenzel, Erin and Boelk, Allyssia and Becker, Jodi and Mocchetti, Italo},
      title = {The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in aging mice.},
      journal = {Neurobiol Aging},
      school = {Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: moccheti@georgetown.edu.},
      year = {2016},
      volume = {46},
      pages = {160--168},
      url = {http://dx.doi.org/10.1016/j.neurobiolaging.2016.07.001},
      doi = {http://doi.org/10.1016/j.neurobiolaging.2016.07.001}
    }
    
    Bikson, M., Grossman, P., Thomas, C., Zannou, A.L., Jiang, J., Adnan, T., Mourdoukoutas, A.P., Kronberg, G., Truong, D., Boggio, P., Brunoni, A.R., Charvet, L., Fregni, F., Fritsch, B., Gillick, B., Hamilton, R.H., Hampstead, B.M., Jankord, R., Kirton, A., Knotkova, H., Liebetanz, D., Liu, A., Loo, C., Nitsche, M.A., Reis, J., Richardson, J.D., Rotenberg, A., Turkeltaub, P.E. & Woods, A.J. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. 2016 Brain StimulSchool: Center for Cognitive Aging and Memory, Institute on Aging, Department of Aging and Geriatric Research, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.  DOI URL 
    Abstract: This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13?A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (?40?min, ?4?milliamperes, ?7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.
    BibTeX:
    @article{BiksonGrossmanThomasEtAl2016,
      author = {Bikson, Marom and Grossman, Pnina and Thomas, Chris and Zannou, Adantchede Louis and Jiang, Jimmy and Adnan, Tatheer and Mourdoukoutas, Antonios P. and Kronberg, Greg and Truong, Dennis and Boggio, Paulo and Brunoni, André R. and Charvet, Leigh and Fregni, Felipe and Fritsch, Brita and Gillick, Bernadette and Hamilton, Roy H. and Hampstead, Benjamin M. and Jankord, Ryan and Kirton, Adam and Knotkova, Helena and Liebetanz, David and Liu, Anli and Loo, Colleen and Nitsche, Michael A. and Reis, Janine and Richardson, Jessica D. and Rotenberg, Alexander and Turkeltaub, Peter E. and Woods, Adam J.},
      title = {Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.},
      journal = {Brain Stimul},
      school = {Center for Cognitive Aging and Memory, Institute on Aging, Department of Aging and Geriatric Research, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.},
      year = {2016},
      url = {http://dx.doi.org/10.1016/j.brs.2016.06.004},
      doi = {http://doi.org/10.1016/j.brs.2016.06.004}
    }
    
    Cameron Craddock, R., S Margulies, D., Bellec, P., Nolan Nichols, B., Alcauter, S., A Barrios, F., Burnod, Y., J Cannistraci, C., Cohen-Adad, J., De Leener, B., Dery, S., Downar, J., Dunlop, K., R Franco, A., Seligman Froehlich, C., J Gerber, A., S Ghosh, S., J Grabowski, T., Hill, S., Sólon Heinsfeld, A., Matthew Hutchison, R., Kundu, P., R Laird, A., Liew, S.-L., J Lurie, D., G McLaren, D., Meneguzzi, F., Mennes, M., Mesmoudi, S., O'Connor, D., H Pasaye, E., Peltier, S., Poline, J.-B., Prasad, G., Fraga Pereira, R., Quirion, P.-O., Rokem, A., S Saad, Z., Shi, Y., C Strother, S., Toro, R., Q Uddin, L., D Van Horn, J., W Van Meter, J., C Welsh, R. & Xu, T. Brainhack: a collaborative workshop for the open neuroscience community. 2016 Gigascience
    Vol. 5, pp. 16School: Center for the Developing Brain, Child Mind Institute, New York, New York, 10022 USA. 
    DOI URL 
    Abstract: Brainhack events offer a novel workshop format with participant-generated content that caters to the rapidly growing open neuroscience community. Including components from hackathons and unconferences, as well as parallel educational sessions, Brainhack fosters novel collaborations around the interests of its attendees. Here we provide an overview of its structure, past events, and example projects. Additionally, we outline current innovations such as regional events and post-conference publications. Through introducing Brainhack to the wider neuroscience community, we hope to provide a unique conference format that promotes the features of collaborative, open science.
    BibTeX:
    @article{CameronCraddockSMarguliesBellecEtAl2016,
      author = {Cameron Craddock, R. and S Margulies, Daniel and Bellec, Pierre and Nolan Nichols, B. and Alcauter, Sarael and A Barrios, Fernando and Burnod, Yves and J Cannistraci, Christopher and Cohen-Adad, Julien and De Leener, Benjamin and Dery, Sebastien and Downar, Jonathan and Dunlop, Katharine and R Franco, Alexandre and Seligman Froehlich, Caroline and J Gerber, Andrew and S Ghosh, Satrajit and J Grabowski, Thomas and Hill, Sean and Sólon Heinsfeld, Anibal and Matthew Hutchison, R. and Kundu, Prantik and R Laird, Angela and Liew, Sook-Lei and J Lurie, Daniel and G McLaren, Donald and Meneguzzi, Felipe and Mennes, Maarten and Mesmoudi, Salma and O'Connor, David and H Pasaye, Erick and Peltier, Scott and Poline, Jean-Baptiste and Prasad, Gautam and Fraga Pereira, Ramon and Quirion, Pierre-Olivier and Rokem, Ariel and S Saad, Ziad and Shi, Yonggang and C Strother, Stephen and Toro, Roberto and Q Uddin, Lucina and D Van Horn, John and W Van Meter, John and C Welsh, Robert and Xu, Ting},
      title = {Brainhack: a collaborative workshop for the open neuroscience community.},
      journal = {Gigascience},
      school = {Center for the Developing Brain, Child Mind Institute, New York, New York, 10022 USA.},
      year = {2016},
      volume = {5},
      pages = {16},
      url = {http://dx.doi.org/10.1186/s13742-016-0121-x},
      doi = {http://doi.org/10.1186/s13742-016-0121-x}
    }
    
    DeWitt, I. & Rauschecker, J.P. Convergent evidence for the causal involvement of~anterior superior temporal gyrus in auditory single-word comprehension. 2016 Cortex
    Vol. 77, pp. 164-166School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: rauschej@georgetown.edu. 
    DOI URL 
    BibTeX:
    @article{DeWittRauschecker2016,
      author = {DeWitt, Iain and Rauschecker, Josef P.},
      title = {Convergent evidence for the causal involvement of~anterior superior temporal gyrus in auditory single-word comprehension.},
      journal = {Cortex},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: rauschej@georgetown.edu.},
      year = {2016},
      volume = {77},
      pages = {164--166},
      url = {http://dx.doi.org/10.1016/j.cortex.2015.08.016},
      doi = {http://doi.org/10.1016/j.cortex.2015.08.016}
    }
    
    Dezfuli, G., Kellar, K.J., Dretchen, K.L., Tizabi, Y., Sahibzada, N. & Gillis, R.A. Evidence for the role of $2* nAChR desensitization in regulating body weight in obese mice. 2016 Neuropharmacology
    Vol. 110(Pt A), pp. 165-174School: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, D.C., USA. Electronic address: gillisr@georgetown.edu. 
    DOI URL 
    Abstract: Nicotine's effect on food intake and body weight has been well documented; however, the relevant receptors underlying these effects have not been firmly established. The purpose of the present study was to: (1) identify the nicotinic acetylcholine receptor (nAChR) subtype involved in food intake and body weight; (2) establish whether food intake and body weight reduction produced by nicotinic drugs are due to activation or desensitization of nAChRs; and, (3) assess the role of the melanocortin system in nicotinic drug effects on food intake and body weight. To identify the nAChR, we tested the effect of sazetidine-A (SAZ-A), a relatively selective ligand of ?2-containing nAChRs, on food intake and body weight in obese mice. SAZ-A (3 mg/kg; SC) administered twice-daily significantly decreased food intake and body weight. To assess whether these effects involved desensitization, SAZ-A was administered to non-obese mice via osmotic pump, which, due to its slow sustained drug delivery method, causes prolonged desensitization. SAZ-A via osmotic pump delivery significantly decreased the gain in body weight and reduced food intake. In contrast, body weight was unaffected by SAZ-A in ?2(-/-) mice or in mice lacking the melanocortin 4 receptor (MC4R). These results indicate that ?2 containing nAChRs are essential to SAZ-A's inhibitory effect on body weight and food intake and engage the melanocortin system.
    BibTeX:
    @article{DezfuliKellarDretchenEtAl2016,
      author = {Dezfuli, Ghazaul and Kellar, Kenneth J. and Dretchen, Kenneth L. and Tizabi, Yousef and Sahibzada, Niaz and Gillis, Richard A.},
      title = {Evidence for the role of $2* nAChR desensitization in regulating body weight in obese mice.},
      journal = {Neuropharmacology},
      school = {Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, D.C., USA. Electronic address: gillisr@georgetown.edu.},
      year = {2016},
      volume = {110},
      number = {Pt A},
      pages = {165--174},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2016.07.020},
      doi = {http://doi.org/10.1016/j.neuropharm.2016.07.020}
    }
    
    DiBattista, A.M., Dumanis, S.B., Newman, J. & Rebeck, G.W. Identification and modification of amyloid-independent phenotypes of APOE4 mice. 2016 Exp Neurol
    Vol. 280, pp. 97-105School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: gwr2@georgetown.edu. 
    DOI URL 
    Abstract: Over 70 million Americans inherit the strongest genetic risk factor for Alzheimer's disease (AD), apolipoprotein E4 (APOE4), but have no course for reducing their risk. The association of non-steroidal anti-inflammatory drug (NSAID) use with reduced risk of AD for APOE4-carriers suggests that NSAIDs may be useful in AD prevention.We identified phenotypes associated with APOE4 in APOE knock-in mice in order to define modifiable measures that correlate with risk of AD.APOE4 mouse brains showed altered post-translational modifications and biochemical distribution of APOE compared to APOE3 mice; these differences were also observed in brains of human APOE4 carriers. Two-month treatment with ibuprofen significantly altered the expression pattern of APOE in APOE4 mice to that of APOE3 mice; PPAR-? agonist pioglitazone also had a significant effect. APOE4 mice also show deficits in dendritic spine density, and ibuprofen and pioglitazone significantly increased dendritic spine density.We report new phenotypes associated with APOE4 in human and APOE knock-in mice and their mitigation with NSAID treatment, through COX-2 inhibition and PPAR-? activation.
    BibTeX:
    @article{DiBattistaDumanisNewmanEtAl2016,
      author = {DiBattista, Amanda M. and Dumanis, Sonya B. and Newman, Joshua and Rebeck, G William},
      title = {Identification and modification of amyloid-independent phenotypes of APOE4 mice.},
      journal = {Exp Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: gwr2@georgetown.edu.},
      year = {2016},
      volume = {280},
      pages = {97--105},
      url = {http://dx.doi.org/10.1016/j.expneurol.2016.04.014},
      doi = {http://doi.org/10.1016/j.expneurol.2016.04.014}
    }
    
    DiBattista, A.M., Heinsinger, N.M. & William Rebeck, G. Alzheimer's Disease Genetic Risk Factor APOE-$4 Also Affects Normal Brain Function. 2016 Curr Alzheimer ResSchool: Department of Neuroscience, Georgetown University, Washington, DC, USA. gwr2@georgetown.edu.   
    Abstract: APOE-?4 is the strongest genetic risk factor for Alzheimer's disease (AD), and is associated with an increase in the levels of amyloid deposition and an early age of onset. Recent data demonstrate that AD pathological changes occur decades before clinical symptoms, raising questions about the precise onset of the disease. Now a convergence of approaches in mice and humans has demonstrated that APOE-?4 affects normal brain function even very early in life in the absence of gross AD pathological changes. Normal mice expressing APOE4 have task-specific spatial learning deficits, as well as reduced NMDAR-dependent signaling and structural changes to presynaptic and postsynaptic compartments in neurons, particularly in hippocampal regions. Young humans possessing APOE-?4 are more adept than APOE-?4 negative individuals at some behavioral tasks, and functional magnetic resonance imaging has shown that inheritance of APOE-?4 has specific effects on medial temporal brain activities. These findings suggest that inheritance of APOE-?4 causes life long changes to the brain that may be related to the late risk of AD. Several possible mechanisms of how APOE-?4 could affect brain neurochemistry, structure, and function are reviewed.
    BibTeX:
    @article{DiBattistaHeinsingerWilliamRebeck2016,
      author = {DiBattista, Amanda M. and Heinsinger, Nicolette M. and William Rebeck, G.},
      title = {Alzheimer's Disease Genetic Risk Factor APOE-$4 Also Affects Normal Brain Function.},
      journal = {Curr Alzheimer Res},
      school = {Department of Neuroscience, Georgetown University, Washington, DC, USA. gwr2@georgetown.edu.},
      year = {2016}
    }
    
    Dye, C.D., Walenski, M., Mostofsky, S.H. & Ullman, M.T. A verbal strength in children with Tourette syndrome? Evidence from a non-word repetition task. 2016 Brain Lang
    Vol. 160, pp. 61-70School: Brain and Language Lab, Department of Neuroscience, Georgetown University, United States. Electronic address: michael@georgetown.edu. 
    DOI URL 
    Abstract: Tourette syndrome (TS) is characterized by motor and vocal tics, and frontal/basal-ganglia abnormalities. Whereas cognitive strengths have been found in other neurodevelopmental disorders, less attention has been paid to strengths in TS, or to verbal strengths in any neurodevelopmental disorder. We examined whether the finding of speeded TS production of rule-governed morphological forms (e.g., "slipped") that involve composition (Walenski, Mostofsky, & Ullman, 2007) might extend to another language domain, phonology. Thirteen children with TS and 14 typically-developing (TD) children performed a non-word repetition task: they repeated legal phonological strings (e.g.,"naichovabe"), a task that taps rule-governed (de)composition. Parallel to the morphology findings, the children with TS showed speeded production, while the two groups had similar accuracy. The results were not explained by potentially confounding factors, including IQ. Overall, the findings suggest that rule-governed grammatical composition may be speeded in TS, perhaps due to frontal/basal-ganglia abnormalities.
    BibTeX:
    @article{DyeWalenskiMostofskyEtAl2016,
      author = {Dye, Cristina D. and Walenski, Matthew and Mostofsky, Stewart H. and Ullman, Michael T.},
      title = {A verbal strength in children with Tourette syndrome? Evidence from a non-word repetition task.},
      journal = {Brain Lang},
      school = {Brain and Language Lab, Department of Neuroscience, Georgetown University, United States. Electronic address: michael@georgetown.edu.},
      year = {2016},
      volume = {160},
      pages = {61--70},
      url = {http://dx.doi.org/10.1016/j.bandl.2016.07.005},
      doi = {http://doi.org/10.1016/j.bandl.2016.07.005}
    }
    
    Erickson, L.C., Rauschecker, J.P. & Turkeltaub, P.E. Meta-analytic connectivity modeling of the human superior temporal sulcus. 2016 Brain Struct FunctSchool: Research Division, MedStar National Rehabilitation Hospital, 102 Irving St NW, Washington, DC, 20010, USA. turkeltp@georgetown.edu.  DOI URL 
    Abstract: The superior temporal sulcus (STS) is a critical region for multiple neural processes in the human brain Hein and Knight (J Cogn Neurosci 20(12): 2125-2136, 2008). To better understand the multiple functions of the STS it would be useful to know more about its consistent functional coactivations with other brain regions. We used the meta-analytic connectivity modeling technique to determine consistent functional coactivation patterns across experiments and behaviors associated with bilateral anterior, middle, and posterior anatomical STS subregions. Based on prevailing models for the cortical organization of audition and language, we broadly hypothesized that across various behaviors the posterior STS (pSTS) would coactivate with dorsal-stream regions, whereas the anterior STS (aSTS) would coactivate with ventral-stream regions. The results revealed distinct coactivation patterns for each STS subregion, with some overlap in the frontal and temporal areas, and generally similar coactivation patterns for the left and right STS. Quantitative comparison of STS subregion coactivation maps demonstrated that the pSTS coactivated more strongly than other STS subregions in the same hemisphere with dorsal-stream regions, such as the inferior parietal lobule (only left pSTS), homotopic pSTS, precentral gyrus and supplementary motor area. In contrast, the aSTS showed more coactivation with some ventral-stream regions, such as the homotopic anterior temporal cortex and left inferior frontal gyrus, pars orbitalis (only right aSTS). These findings demonstrate consistent coactivation maps across experiments and behaviors for different anatomical STS subregions, which may help future studies consider various STS functions in the broader context of generalized coactivations for individuals with and without neurological disorders.
    BibTeX:
    @article{EricksonRauscheckerTurkeltaub2016,
      author = {Erickson, Laura C. and Rauschecker, Josef P. and Turkeltaub, Peter E.},
      title = {Meta-analytic connectivity modeling of the human superior temporal sulcus.},
      journal = {Brain Struct Funct},
      school = {Research Division, MedStar National Rehabilitation Hospital, 102 Irving St NW, Washington, DC, 20010, USA. turkeltp@georgetown.edu.},
      year = {2016},
      url = {http://dx.doi.org/10.1007/s00429-016-1215-z},
      doi = {http://doi.org/10.1007/s00429-016-1215-z}
    }
    
    Giordano, J. Toward an operational neuroethical risk analysis and mitigation paradigm for emerging neuroscience and technology (neuroS/T). 2016 Exp NeurolSchool: eservoir Road, Bldg. D, Rm. 238, Washington, DC 20057, USA. Electronic address: james.giordano@georgetown.edu.  DOI URL 
    Abstract: Research in neuroscience and neurotechnology (neuroS/T) is progressing at a rapid pace with translational applications both in medicine, and more widely in the social milieu. Current and projected neuroS/T research and its applications evoke a number of neuroethicolegal and social issues (NELSI). This paper defines inherent and derivative NELSI of current and near-term neuroS/T development and engagement, and provides an overview of our group's ongoing work to develop a systematized approach to their address. Our proposed operational neuroethical risk assessment and mitigation paradigm (ONRAMP) is presented, which entails querying, framing, and modeling patterns and trajectories of neuroS/T research and translational uses, and the NELSI generated by such advancements and their applications. Extant ethical methods are addressed, with suggestion toward possible revision or re-formulation to meet the needs and exigencies fostered by neuroS/T and resultant NELSI in multi-cultural contexts. The relevance and importance of multi-disciplinary expertise in focusing upon NELSI is discussed, and the need for neuroethics education toward cultivating such a cadre of expertise is emphasized.
    BibTeX:
    @article{Giordano2016,
      author = {Giordano, James},
      title = {Toward an operational neuroethical risk analysis and mitigation paradigm for emerging neuroscience and technology (neuroS/T).},
      journal = {Exp Neurol},
      school = {eservoir Road, Bldg. D, Rm. 238, Washington, DC 20057, USA. Electronic address: james.giordano@georgetown.edu.},
      year = {2016},
      url = {http://dx.doi.org/10.1016/j.expneurol.2016.07.016},
      doi = {http://doi.org/10.1016/j.expneurol.2016.07.016}
    }
    
    Glezer, L.S., Eden, G., Jiang, X., Luetje, M., Napoliello, E., Kim, J. & Riesenhuber, M. Uncovering phonological and orthographic selectivity across the reading network using fMRI-RA. 2016 Neuroimage
    Vol. 138, pp. 248-256School: Department of Neuroscience, Georgetown University Medical Center, 3800 Reservoir Rd. NW, Washington, District of Columbia 20007, USA. 
    DOI URL 
    Abstract: Reading has been shown to rely on a dorsal brain circuit involving the temporoparietal cortex (TPC) for grapheme-to-phoneme conversion of novel words (Pugh et al., 2001), and a ventral stream involving left occipitotemporal cortex (OTC) (in particular in the so-called "visual word form area", VWFA) for visual identification of familiar words. In addition, portions of the inferior frontal cortex (IFC) have been posited to be an output of the dorsal reading pathway involved in phonology. While this dorsal versus ventral dichotomy for phonological and orthographic processing of words is widely accepted, it is not known if these brain areas are actually strictly sensitive to orthographic or phonological information. Using an fMRI rapid adaptation technique we probed the selectivity of the TPC, OTC, and IFC to orthographic and phonological features during single word reading. We found in two independent experiments using different task conditions in adult normal readers, that the TPC is exclusively sensitive to phonology and the VWFA in the OTC is exclusively sensitive to orthography. The dorsal IFC (BA 44), however, showed orthographic but not phonological selectivity. These results support the theory that reading involves a specific phonological-based temporoparietal region and a specific orthographic-based ventral occipitotemporal region. The dorsal IFC, however, was not sensitive to phonological processing, suggesting a more complex role for this region.
    BibTeX:
    @article{GlezerEdenJiangEtAl2016,
      author = {Glezer, Laurie S. and Eden, Guinevere and Jiang, Xiong and Luetje, Megan and Napoliello, Eileen and Kim, Judy and Riesenhuber, Maximilian},
      title = {Uncovering phonological and orthographic selectivity across the reading network using fMRI-RA.},
      journal = {Neuroimage},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3800 Reservoir Rd. NW, Washington, District of Columbia 20007, USA.},
      year = {2016},
      volume = {138},
      pages = {248--256},
      url = {http://dx.doi.org/10.1016/j.neuroimage.2016.05.072},
      doi = {http://doi.org/10.1016/j.neuroimage.2016.05.072}
    }
    
    Green, A.E., Spiegel, K.A., Giangrande, E.J., Weinberger, A.B., Gallagher, N.M. & Turkeltaub, P.E. Thinking Cap Plus Thinking Zap: tDCS of Frontopolar Cortex Improves Creative Analogical Reasoning and Facilitates Conscious Augmentation of State Creativity in Verb Generation. 2016 Cereb CortexSchool: Department of Neurology, Georgetown University Medical Center, Washington, DC, USA Research Division, MedStar National Rehabilitation Hospital, Washington, DC, USA.  DOI URL 
    Abstract: Recent neuroimaging evidence indicates neural mechanisms that support transient improvements in creative performance (augmented state creativity) in response to cognitive interventions (creativity cueing). Separately, neural interventions via tDCS show encouraging potential for modulating neuronal function during creative performance. If cognitive and neural interventions are separately effective, can they be combined? Does state creativity augmentation represent "real" creativity, or do interventions simply yield divergence by diminishing meaningfulness/appropriateness? Can augmenting state creativity bolster creative reasoning that supports innovation, particularly analogical reasoning? To address these questions, we combined tDCS with creativity cueing. Testing a regionally specific hypothesis from neuroimaging, high-definition tDCS-targeted frontopolar cortex activity recently shown to predict state creativity augmentation. In a novel analogy finding task, participants under tDCS formulated substantially more creative analogical connections in a large matrix search space (creativity indexed via latent semantic analysis). Critically, increased analogical creativity was not due to diminished accuracy in discerning valid analogies, indicating "real" creativity rather than inappropriate divergence. A simpler relational creativity paradigm (modified verb generation) revealed a tDCS-by-cue interaction; tDCS further enhanced creativity cue-related increases in semantic distance. Findings point to the potential of noninvasive neuromodulation to enhance creative relational cognition, including augmentation of the deliberate effort to formulate connections between distant concepts.
    BibTeX:
    @article{GreenSpiegelGiangrandeEtAl2016,
      author = {Green, Adam E. and Spiegel, Katherine A. and Giangrande, Evan J. and Weinberger, Adam B. and Gallagher, Natalie M. and Turkeltaub, Peter E.},
      title = {Thinking Cap Plus Thinking Zap: tDCS of Frontopolar Cortex Improves Creative Analogical Reasoning and Facilitates Conscious Augmentation of State Creativity in Verb Generation.},
      journal = {Cereb Cortex},
      school = {Department of Neurology, Georgetown University Medical Center, Washington, DC, USA Research Division, MedStar National Rehabilitation Hospital, Washington, DC, USA.},
      year = {2016},
      url = {http://dx.doi.org/10.1093/cercor/bhw080},
      doi = {http://doi.org/10.1093/cercor/bhw080}
    }
    
    Jiang, X., Barasky, R., Olsen, H., Riesenhuber, M. & Magnus, M. Behavioral and neuroimaging evidence for impaired executive function in "cognitively normal" older HIV-infected adults. 2016 AIDS Care
    Vol. 28(4), pp. 436-440School: b Department of Epidemiology and Biostatistics , The George Washington University School of Public Health and Health Services , Washington , DC , USA. 
    DOI URL 
    Abstract: The increased prevalence of HIV among adults >50 years underscores the importance of improving our understanding of mechanisms causing HIV-associated neurocognitive disorders (HAND). Identifying novel and noninvasive diagnostic predictors of HAND prior to clinical manifestation is critical to ultimately identifying means of preventing progression to symptomatic HAND. Here, using a task-switching paradigm, in which subjects were cued (unpredictably) to perform a face-gender or a word-semantic task on superimposed face and word images, we examined the behavioral and neural profile of impaired cognitive control in older HIV?+?adults (N?=?14, 9 HIV+). Functional magnetic resonance imaging (fMRI) and behavioral data were acquired while subjects were performing the face-gender or word-semantic task. We found that, despite comparable performance in standard neuropsychology tests that are designed to probe executive deficits, HIV-infected participants were significantly slower than uninfected controls in adapting to change in task demand, and the behavioral impairments can be quantitatively related to difference in fMRI signal at the dorsal anterior cingulate cortex (ACC). Due to the limited sample size of this hypothesis-generating study, we should take caution with these findings and future studies with a large and better matched sample size are needed. However, these rather novel findings in this study have a few important implications: first, the prevalence of cognitive impairments in HIV+ older adults might be even higher than previously proposed; second, ACC (in particularly its dorsal region) might be one of the key regions underlying cognitive impairments (in particularly executive functions) in HIV; and third, it might be beneficial to adopt paradigms developed and validated in cognitive neuroscience to study HAND, as these techniques might be more sensitive to some aspects of HIV-associated neurocognitive impairments than standard neuropsychology tests.
    BibTeX:
    @article{JiangBaraskyOlsenEtAl2016,
      author = {Jiang, Xiong and Barasky, Rebecca and Olsen, Halli and Riesenhuber, Maximilian and Magnus, Manya},
      title = {Behavioral and neuroimaging evidence for impaired executive function in "cognitively normal" older HIV-infected adults.},
      journal = {AIDS Care},
      school = {b Department of Epidemiology and Biostatistics , The George Washington University School of Public Health and Health Services , Washington , DC , USA.},
      year = {2016},
      volume = {28},
      number = {4},
      pages = {436--440},
      url = {http://dx.doi.org/10.1080/09540121.2015.1112347},
      doi = {http://doi.org/10.1080/09540121.2015.1112347}
    }
    
    Leaver, A.M. & Rauschecker, J.P. Functional Topography of Human Auditory Cortex. 2016 J Neurosci
    Vol. 36(4), pp. 1416-1428School: Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, Institute for Advanced Study, Technische Universit?t M?nchen, D-85748 Garching, Germany. 
    DOI URL 
    Abstract: Functional and anatomical studies have clearly demonstrated that auditory cortex is populated by multiple subfields. However, functional characterization of those fields has been largely the domain of animal electrophysiology, limiting the extent to which human and animal research can inform each other. In this study, we used high-resolution functional magnetic resonance imaging to characterize human auditory cortical subfields using a variety of low-level acoustic features in the spectral and temporal domains. Specifically, we show that topographic gradients of frequency preference, or tonotopy, extend along two axes in human auditory cortex, thus reconciling historical accounts of a tonotopic axis oriented medial to lateral along Heschl's gyrus and more recent findings emphasizing tonotopic organization along the anterior-posterior axis. Contradictory findings regarding topographic organization according to temporal modulation rate in acoustic stimuli, or "periodotopy," are also addressed. Although isolated subregions show a preference for high rates of amplitude-modulated white noise (AMWN) in our data, large-scale "periodotopic" organization was not found. Organization by AM rate was correlated with dominant pitch percepts in AMWN in many regions. In short, our data expose early auditory cortex chiefly as a frequency analyzer, and spectral frequency, as imposed by the sensory receptor surface in the cochlea, seems to be the dominant feature governing large-scale topographic organization across human auditory cortex.In this study, we examine the nature of topographic organization in human auditory cortex with fMRI. Topographic organization by spectral frequency (tonotopy) extended in two directions: medial to lateral, consistent with early neuroimaging studies, and anterior to posterior, consistent with more recent reports. Large-scale organization by rates of temporal modulation (periodotopy) was correlated with confounding spectral content of amplitude-modulated white-noise stimuli. Together, our results suggest that the organization of human auditory cortex is driven primarily by its response to spectral acoustic features, and large-scale periodotopy spanning across multiple regions is not supported. This fundamental information regarding the functional organization of early auditory cortex will inform our growing understanding of speech perception and the processing of other complex sounds.
    BibTeX:
    @article{LeaverRauschecker2016,
      author = {Leaver, Amber M. and Rauschecker, Josef P.},
      title = {Functional Topography of Human Auditory Cortex.},
      journal = {J Neurosci},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, Institute for Advanced Study, Technische Universit?t M?nchen, D-85748 Garching, Germany.},
      year = {2016},
      volume = {36},
      number = {4},
      pages = {1416--1428},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.0226-15.2016},
      doi = {http://doi.org/10.1523/JNEUROSCI.0226-15.2016}
    }
    
    Leaver, A.M., Turesky, T.K., Seydell-Greenwald, A., Morgan, S., Kim, H.J. & Rauschecker, J.P. Intrinsic network activity in tinnitus investigated using functional MRI. 2016 Hum Brain Mapp
    Vol. 37(8), pp. 2717-2735School: Institute for Advanced Study, TU Munich, Germany. 
    DOI URL 
    Abstract: Tinnitus is an increasingly common disorder in which patients experience phantom auditory sensations, usually ringing or buzzing in the ear. Tinnitus pathophysiology has been repeatedly shown to involve both auditory and non-auditory brain structures, making network-level studies of tinnitus critical. In this magnetic resonance imaging (MRI) study, two resting-state functional connectivity (RSFC) approaches were used to better understand functional network disturbances in tinnitus. First, we demonstrated tinnitus-related reductions in RSFC between specific brain regions and resting-state networks (RSNs), defined by independent components analysis (ICA) and chosen for their overlap with structures known to be affected in tinnitus. Then, we restricted ICA to data from tinnitus patients, and identified one RSN not apparent in control data. This tinnitus RSN included auditory-sensory regions like inferior colliculus and medial Heschl's gyrus, as well as classically non-auditory regions like the mediodorsal nucleus of the thalamus, striatum, lateral prefrontal, and orbitofrontal cortex. Notably, patients' reported tinnitus loudness was positively correlated with RSFC between the mediodorsal nucleus and the tinnitus RSN, indicating that this network may underlie the auditory-sensory experience of tinnitus. These data support the idea that tinnitus involves network dysfunction, and further stress the importance of communication between auditory-sensory and fronto-striatal circuits in tinnitus pathophysiology. Hum Brain Mapp 37:2717-2735, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    BibTeX:
    @article{LeaverTureskySeydell-GreenwaldEtAl2016,
      author = {Leaver, Amber M. and Turesky, Ted K. and Seydell-Greenwald, Anna and Morgan, Susan and Kim, Hung J. and Rauschecker, Josef P.},
      title = {Intrinsic network activity in tinnitus investigated using functional MRI.},
      journal = {Hum Brain Mapp},
      school = {Institute for Advanced Study, TU Munich, Germany.},
      year = {2016},
      volume = {37},
      number = {8},
      pages = {2717--2735},
      url = {http://dx.doi.org/10.1002/hbm.23204},
      doi = {http://doi.org/10.1002/hbm.23204}
    }
    
    Lee, N.J., Song, J.M., Cho, H.-J., Sung, Y.M., Lee, T., Chung, A., Hong, S.-H., Cifelli, J.L., Rubinshtein, M., Habib, L.K., Capule, C.C., Turner, R.S., Pak, D.T.S., Yang, J. & Hoe, H.-S. Hexa (ethylene glycol) derivative of benzothiazole aniline promotes dendritic spine formation through the RasGRF1-Ras dependent pathway. 2016 Biochim Biophys Acta
    Vol. 1862(2), pp. 284-295School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea. Electronic address: sookhoe72@kbri.re.kr. 
    DOI URL 
    Abstract: Our recent study demonstrated that an amyloid-β binding molecule, BTA-EG4, increases dendritic spine number via Ras-mediated signaling. To potentially optimize the potency of the BTA compounds, we synthesized and evaluated an amyloid-β binding analog of BTA-EG4 with increased solubility in aqueous solution, BTA-EG6. We initially examined the effects of BTA-EG6 on dendritic spine formation and found that BTA-EG6-treated primary hippocampal neurons had significantly increased dendritic spine number compared to control treatment. In addition, BTA-EG6 significantly increased the surface level of AMPA receptors. Upon investigation into the molecular mechanism by which BTA-EG6 promotes dendritic spine formation, we found that BTA-EG6 may exert its effects on spinogenesis via RasGRF1-ERK signaling, with potential involvement of other spinogenesis-related proteins such as Cdc42 and CDK5. Taken together, our data suggest that BTA-EG6 boosts spine and synapse number, which may have a beneficial effect of enhancing neuronal and synaptic function in the normal healthy brain.
    BibTeX:
    @article{LeeSongChoEtAl2016,
      author = {Lee, Nathanael J. and Song, Jung Min and Cho, Hyun-Ji and Sung, You Me and Lee, Taehee and Chung, Andrew and Hong, Sung-Ha and Cifelli, Jessica L. and Rubinshtein, Mark and Habib, Lila K. and Capule, Christina C. and Turner, R Scott and Pak, Daniel T S. and Yang, Jerry and Hoe, Hyang-Sook},
      title = {Hexa (ethylene glycol) derivative of benzothiazole aniline promotes dendritic spine formation through the RasGRF1-Ras dependent pathway.},
      journal = {Biochim Biophys Acta},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), Cheomdan-ro, Dong-gu, Daegu 701-300, Republic of Korea. Electronic address: sookhoe72@kbri.re.kr.},
      year = {2016},
      volume = {1862},
      number = {2},
      pages = {284--295},
      url = {http://dx.doi.org/10.1016/j.bbadis.2015.12.007},
      doi = {http://doi.org/10.1016/j.bbadis.2015.12.007}
    }
    
    Li, Y., Partridge, J., Berger, C., Sepulveda-Rodriguez, A., Vicini, S. & Conant, K. Dopamine increases NMDA-stimulated calcium flux in striatopallidal neurons through a matrix metalloproteinase-dependent mechanism. 2016 Eur J Neurosci
    Vol. 43(2), pp. 194-203School: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China. 
    DOI URL 
    BibTeX:
    @article{LiPartridgeBergerEtAl2016,
      author = {Li, Yan and Partridge, John and Berger, Carissa and Sepulveda-Rodriguez, Alberto and Vicini, Stefano and Conant, Katherine},
      title = {Dopamine increases NMDA-stimulated calcium flux in striatopallidal neurons through a matrix metalloproteinase-dependent mechanism.},
      journal = {Eur J Neurosci},
      school = {State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.},
      year = {2016},
      volume = {43},
      number = {2},
      pages = {194--203},
      url = {http://dx.doi.org/10.1111/ejn.13146},
      doi = {http://doi.org/10.1111/ejn.13146}
    }
    
    Lussier, A.L., Weeber, E.J. & Rebeck, G.W. Reelin Proteolysis Affects Signaling Related to Normal Synapse Function and Neurodegeneration. 2016 Front Cell Neurosci
    Vol. 10, pp. 75School: Department of Neuroscience, Georgetown University Washington, DC, USA. 
    DOI URL 
    Abstract: Reelin is a neurodevelopmental protein important in adult synaptic plasticity and learning and memory. Recent evidence points to the importance for Reelin proteolysis in normal signaling and in cognitive function. Support for the dysfunction of Reelin proteolysis in neurodegeneration and cognitive dysfunction comes from postmortem analysis of Alzheimer's diseases (AD) tissues including cerebral spinal fluid (CSF), showing that levels of Reelin fragments are altered in AD compared to control. Potential key proteases involved in Reelin proteolysis have recently been defined, identifying processes that could be altered in neurodegeneration. Introduction of full-length Reelin and its proteolytic fragments into several mouse models of neurodegeneration and neuropsychiatric disorders quickly promote learning and memory. These findings support a role for Reelin in learning and memory and suggest further understanding of these processes are important to harness the potential of this pathway in treating cognitive symptoms in neuropsychiatric and neurodegenerative diseases.
    BibTeX:
    @article{LussierWeeberRebeck2016,
      author = {Lussier, April L. and Weeber, Edwin J. and Rebeck, G William},
      title = {Reelin Proteolysis Affects Signaling Related to Normal Synapse Function and Neurodegeneration.},
      journal = {Front Cell Neurosci},
      school = {Department of Neuroscience, Georgetown University Washington, DC, USA.},
      year = {2016},
      volume = {10},
      pages = {75},
      url = {http://dx.doi.org/10.3389/fncel.2016.00075},
      doi = {http://doi.org/10.3389/fncel.2016.00075}
    }
    
    Miles, S.A., Miranda, R.A. & Ullman, M.T. Sex Differences in Music: A Female Advantage at Recognizing Familiar Melodies. 2016 Front Psychol
    Vol. 7, pp. 278School: Brain and Language Laboratory, Department of Neuroscience, Georgetown University, Washington DC, USA. 
    DOI URL 
    Abstract: Although sex differences have been observed in various cognitive domains, there has been little work examining sex differences in the cognition of music. We tested the prediction that women would be better than men at recognizing familiar melodies, since memories of specific melodies are likely to be learned (at least in part) by declarative memory, which shows female advantages. Participants were 24 men and 24 women, with half musicians and half non-musicians in each group. The two groups were matched on age, education, and various measures of musical training. Participants were presented with well-known and novel melodies, and were asked to indicate their recognition of familiar melodies as rapidly as possible. The women were significantly faster than the men in responding, with a large effect size. The female advantage held across musicians and non-musicians, and across melodies with and without commonly associated lyrics, as evidenced by an absence of interactions between sex and these factors. Additionally, the results did not seem to be explained by sex differences in response biases, or in basic motor processes as tested in a control task. Though caution is warranted given that this is the first study to examine sex differences in familiar melody recognition, the results are consistent with the hypothesis motivating our prediction, namely that declarative memory underlies knowledge about music (particularly about familiar melodies), and that the female advantage at declarative memory may thus lead to female advantages in music cognition (particularly at familiar melody recognition). Additionally, the findings argue against the view that female advantages at tasks involving verbal (or verbalizable) material are due solely to a sex difference specific to the verbal domain. Further, the results may help explain previously reported cognitive commonalities between music and language: since declarative memory also underlies language, such commonalities may be partly due to a common dependence on this memory system. More generally, because declarative memory is well studied at many levels, evidence that music cognition depends on this system may lead to a powerful research program generating a wide range of novel predictions for the neurocognition of music, potentially advancing the field.
    BibTeX:
    @article{MilesMirandaUllman2016,
      author = {Miles, Scott A. and Miranda, Robbin A. and Ullman, Michael T.},
      title = {Sex Differences in Music: A Female Advantage at Recognizing Familiar Melodies.},
      journal = {Front Psychol},
      school = {Brain and Language Laboratory, Department of Neuroscience, Georgetown University, Washington DC, USA.},
      year = {2016},
      volume = {7},
      pages = {278},
      url = {http://dx.doi.org/10.3389/fpsyg.2016.00278},
      doi = {http://doi.org/10.3389/fpsyg.2016.00278}
    }
    
    Orefice, L.L., Shih, C.-C., Xu, H., Waterhouse, E.G. & Xu, B. Control of spine maturation and pruning through proBDNF synthesized and released in dendrites. 2016 Mol Cell Neurosci
    Vol. 71, pp. 66-79School: Department of Neuroscience, The Scripps Research Institute Florida, 130 Scripps Way, Jupiter, FL 33458, USA; Department of Pharmacology and Physiology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA. Electronic address: bxu@scripps.edu. 
    DOI URL 
    Abstract: Excess synapses formed during early postnatal development are pruned over an extended period, while the remaining synapses mature. Synapse pruning is critical for activity-dependent refinement of neuronal connections and its dysregulation has been found in neurodevelopmental disorders such as autism spectrum disorders; however, the mechanism underlying synapse pruning remains largely unknown. As dendritic spines are the postsynaptic sites for the vast majority of excitatory synapses, spine maturation and pruning are indicators for maturation and elimination of these synapses. Our previous studies have found that dendritically localized mRNA for brain-derived neurotrophic factor (BDNF) regulates spine maturation and pruning. Here we investigated the mechanism by which dendritic Bdnf mRNA, but not somatically restricted Bdnf mRNA, promotes spine maturation and pruning. We found that neuronal activity stimulates both translation of dendritic Bdnf mRNA and secretion of its translation product mainly as proBDNF. The secreted proBDNF promotes spine maturation and pruning, and its effect on spine pruning is in part mediated by the p75(NTR) receptor via RhoA activation. Furthermore, some proBDNF is extracellularly converted to mature BDNF and then promotes maturation of stimulated spines by activating Rac1 through the TrkB receptor. In contrast, translation of somatic Bdnf mRNA and the release of its translation product mainly as mature BDNF are independent of action potentials. These results not only reveal a biochemical pathway regulating synapse pruning, but also suggest that BDNF synthesized in the soma and dendrites is released through distinct secretory pathways.
    BibTeX:
    @article{OreficeShihXuEtAl2016,
      author = {Orefice, Lauren L. and Shih, Chien-Cheng and Xu, Haifei and Waterhouse, Emily G. and Xu, Baoji},
      title = {Control of spine maturation and pruning through proBDNF synthesized and released in dendrites.},
      journal = {Mol Cell Neurosci},
      school = {Department of Neuroscience, The Scripps Research Institute Florida, 130 Scripps Way, Jupiter, FL 33458, USA; Department of Pharmacology and Physiology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA. Electronic address: bxu@scripps.edu.},
      year = {2016},
      volume = {71},
      pages = {66--79},
      url = {http://dx.doi.org/10.1016/j.mcn.2015.12.010},
      doi = {http://doi.org/10.1016/j.mcn.2015.12.010}
    }
    
    Partridge, J.G., Forcelli, P.A., Luo, R., Cashdan, J.M., Schulkin, J., Valentino, R.J. & Vicini, S. Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis. 2016 Neuropharmacology
    Vol. 107, pp. 239-250School: Physiology, Georgetown University School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Corticotrophin Releasing Factor (CRF) is a critical stress-related neuropeptide in major output pathways of the amygdala, including the central nucleus (CeA), and in a key projection target of the CeA, the bed nucleus of the stria terminalis (BnST). While progress has been made in understanding the contributions and characteristics of CRF as a neuropeptide in rodent behavior, little attention has been committed to determine the properties and synaptic physiology of specific populations of CRF-expressing (CRF(+)) and non-expressing (CRF(-)) neurons in the CeA and BnST. Here, we fill this gap by electrophysiologically characterizing distinct neuronal subtypes in CeA and BnST. Crossing tdTomato or channelrhodopsin-2 (ChR2-YFP) reporter mice to those expressing Cre-recombinase under the CRF promoter allowed us to identify and manipulate CRF(+) and CRF(-) neurons in CeA and BnST, the two largest areas with fluorescently labeled neurons in these mice. We optogenetically activated CRF(+) neurons to elicit action potentials or synaptic responses in CRF(+) and CRF(-) neurons. We found that GABA is the predominant co-transmitter in CRF(+) neurons within the CeA and BnST. CRF(+) neurons are highly interconnected with CRF(-) neurons and to a lesser extent with CRF(+) neurons. CRF(+) and CRF(-) neurons differentially express tonic GABA currents. Chronic, unpredictable stress increase the amplitude of evoked IPSCs and connectivity between CRF(+) neurons, but not between CRF(+) and CRF(-) neurons in both regions. We propose that reciprocal inhibition of interconnected neurons controls CRF(+) output in these nuclei.
    BibTeX:
    @article{PartridgeForcelliLuoEtAl2016,
      author = {Partridge, John G. and Forcelli, Patrick A. and Luo, Ruixi and Cashdan, Jonah M. and Schulkin, Jay and Valentino, Rita J. and Vicini, Stefano},
      title = {Stress increases GABAergic neurotransmission in CRF neurons of the central amygdala and bed nucleus stria terminalis.},
      journal = {Neuropharmacology},
      school = { Physiology, Georgetown University School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA.},
      year = {2016},
      volume = {107},
      pages = {239--250},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2016.03.029},
      doi = {http://doi.org/10.1016/j.neuropharm.2016.03.029}
    }
    
    Queenan, B.N., Lee, K.J., Tan, H., Huganir, R.L., Vicini, S. & Pak, D.T.S. Mapping homeostatic synaptic plasticity using cable properties of dendrites. 2016 Neuroscience
    Vol. 315, pp. 206-216School: Physiology, Georgetown University Medical Center, Washington, DC, United States; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, United States. Electronic address: Daniel.Pak@georgetown.edu. 
    DOI URL 
    Abstract: When chronically silenced, cortical and hippocampal neurons homeostatically upregulate excitatory synaptic function. However, the subcellular position of such changes on the dendritic tree is not clear. We exploited the cable-filtering properties of dendrites to derive a parameter, the dendritic filtering index (DFI), to map the spatial distribution of synaptic currents. Our analysis indicates that young rat cortical neurons globally scale AMPA receptor-mediated currents, while mature hippocampal neurons do not, revealing distinct homeostatic strategies between brain regions and developmental stages. The DFI presents a useful tool for mapping the dendritic origin of synaptic currents and the location of synaptic plasticity changes.
    BibTeX:
    @article{QueenanLeeTanEtAl2016,
      author = {Queenan, B. N. and Lee, K. J. and Tan, H. and Huganir, R. L. and Vicini, S. and Pak, D T S.},
      title = {Mapping homeostatic synaptic plasticity using cable properties of dendrites.},
      journal = {Neuroscience},
      school = { Physiology, Georgetown University Medical Center, Washington, DC, United States; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC, United States. Electronic address: Daniel.Pak@georgetown.edu.},
      year = {2016},
      volume = {315},
      pages = {206--216},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2015.12.017},
      doi = {http://doi.org/10.1016/j.neuroscience.2015.12.017}
    }
    
    Riedl, V., Utz, L., Castrillón, G., Grimmer, T., Rauschecker, J.P., Ploner, M., Friston, K.J., Drzezga, A. & Sorg, C. Metabolic connectivity mapping reveals effective connectivity in the resting human brain. 2016 Proc Natl Acad Sci U S A
    Vol. 113(2), pp. 428-433School: Department of Neuroradiology, Klinikum rechts der Isar, Technischen Universitaet Muenchen, 81675 Muenchen, Germany; Neuroimaging Center, Klinikum Rechts der Isar, Technischen Universitaet Muenchen, 81675 Muenchen, Germany; Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technischen Universitaet Muenchen, 81675 Muenchen, Germany; 
    DOI URL 
    Abstract: Directionality of signaling among brain regions provides essential information about human cognition and disease states. Assessing such effective connectivity (EC) across brain states using functional magnetic resonance imaging (fMRI) alone has proven difficult, however. We propose a novel measure of EC, termed metabolic connectivity mapping (MCM), that integrates undirected functional connectivity (FC) with local energy metabolism from fMRI and positron emission tomography (PET) data acquired simultaneously. This method is based on the concept that most energy required for neuronal communication is consumed postsynaptically, i.e., at the target neurons. We investigated MCM and possible changes in EC within the physiological range using "eyes open" versus "eyes closed" conditions in healthy subjects. Independent of condition, MCM reliably detected stable and bidirectional communication between early and higher visual regions. Moreover, we found stable top-down signaling from a frontoparietal network including frontal eye fields. In contrast, we found additional top-down signaling from all major clusters of the salience network to early visual cortex only in the eyes open condition. MCM revealed consistent bidirectional and unidirectional signaling across the entire cortex, along with prominent changes in network interactions across two simple brain states. We propose MCM as a novel approach for inferring EC from neuronal energy metabolism that is ideally suited to study signaling hierarchies in the brain and their defects in brain disorders.
    BibTeX:
    @article{RiedlUtzCastrillonEtAl2016,
      author = {Riedl, Valentin and Utz, Lukas and Castrillón, Gabriel and Grimmer, Timo and Rauschecker, Josef P. and Ploner, Markus and Friston, Karl J. and Drzezga, Alexander and Sorg, Christian},
      title = {Metabolic connectivity mapping reveals effective connectivity in the resting human brain.},
      journal = {Proc Natl Acad Sci U S A},
      school = {Department of Neuroradiology, Klinikum rechts der Isar, Technischen Universitaet Muenchen, 81675 Muenchen, Germany; Neuroimaging Center, Klinikum Rechts der Isar, Technischen Universitaet Muenchen, 81675 Muenchen, Germany; Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technischen Universitaet Muenchen, 81675 Muenchen, Germany;},
      year = {2016},
      volume = {113},
      number = {2},
      pages = {428--433},
      url = {http://dx.doi.org/10.1073/pnas.1513752113},
      doi = {http://doi.org/10.1073/pnas.1513752113}
    }
    
    Soper, C., Wicker, E., Kulick, C.V., N'Gouemo, P. & Forcelli, P.A. Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks. 2016 Neurobiol Dis
    Vol. 87, pp. 102-115School: Physiology, Georgetown University, Washington, DC 20007; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007. Electronic address: Paf22@georgetown.edu. 
    DOI URL 
    Abstract: Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures. DLSC activation likewise attenuated seizures evoked by gamma butyrolactone (thalamocortical/absence seizures), or acoustic stimulation of genetically epilepsy prone rates (brainstem seizures). Anticonvulsant effects were seen with stimulation frequencies as low as 5 Hz. Unlike previous applications of optogenetics for the control of seizures, activation of DLSC exerted broad-spectrum anticonvulsant actions, attenuating seizures originating in diverse and distal brain networks. These data indicate that DLSC is a promising target for optogenetic control of epilepsy.
    BibTeX:
    @article{SoperWickerKulickEtAl2016,
      author = {Soper, Colin and Wicker, Evan and Kulick, Catherine V. and N'Gouemo, Prosper and Forcelli, Patrick A.},
      title = {Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks.},
      journal = {Neurobiol Dis},
      school = { Physiology, Georgetown University, Washington, DC 20007; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20007. Electronic address: Paf22@georgetown.edu.},
      year = {2016},
      volume = {87},
      pages = {102--115},
      url = {http://dx.doi.org/10.1016/j.nbd.2015.12.012},
      doi = {http://doi.org/10.1016/j.nbd.2015.12.012}
    }
    
    Subiaul, F., Patterson, E.M. & Barr, R. The cognitive structure of goal emulation during the preschool years. 2016 Br J Dev Psychol
    Vol. 34(1), pp. 132-149School: Department of Psychology, Georgetown University, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: Humans excel at mirroring both others' actions (imitation) as well as others' goals and intentions (emulation). As most research has focused on imitation, here we focus on how social and asocial learning predict the development of goal emulation. We tested 215 preschool children on two social conditions (imitation, emulation) and two asocial conditions (trial-and-error and recall) using two touch screen tasks. The tasks involved responding to either three different pictures in a specific picture order (Cognitive: apple?boy?cat) or three identical pictures in a specific spatial order (Motor-Spatial: up?down?right). Generalized linear models demonstrated that during the preschool years, Motor-Spatial emulation is associated with social and asocial learning, while cognitive emulation is associated only with social learning, including motor-spatial emulation and multiple forms of imitation. This result contrasts with those from a previous study using this same data set showing that motor-spatial and cognitive imitation were neither associated with one another nor, generally, predicted by other forms of social or asocial learning. Together, these results suggests that while developmental changes in imitation are associated with multiple - specialized - mechanisms, developmental changes in emulation are associated with age-related changes and a more unitary, domain-general mechanism that receives input from several different cognitive and learning processes, including some that may not necessarily be specialized for social learning.
    BibTeX:
    @article{SubiaulPattersonBarr2016,
      author = {Subiaul, Francys and Patterson, Eric M. and Barr, Rachel},
      title = {The cognitive structure of goal emulation during the preschool years.},
      journal = {Br J Dev Psychol},
      school = {Department of Psychology, Georgetown University, Washington, District of Columbia, USA.},
      year = {2016},
      volume = {34},
      number = {1},
      pages = {132--149},
      url = {http://dx.doi.org/10.1111/bjdp.12111},
      doi = {http://doi.org/10.1111/bjdp.12111}
    }
    
    Turkeltaub, P.E., Swears, M.K., D'Mello, A.M. & Stoodley, C.J. Cerebellar tDCS as a novel treatment for aphasia? Evidence from behavioral and resting-state functional connectivity data in healthy adults. 2016 Restor Neurol NeurosciSchool: Center for Behavioral Neuroscience, American University, Washington D.C., USA.  DOI URL 
    Abstract: Aphasia is an acquired deficit in the ability to communicate through language. Noninvasive neuromodulation offers the potential to boost neural function and recovery, yet the optimal site of neuromodulation for aphasia has yet to be established. The right posterolateral cerebellum is involved in multiple language functions, interconnects with left-hemisphere language cortices, and is crucial for optimization of function and skill acquisition, suggesting that cerebellar neuromodulation could enhance aphasia rehabilitation.To provide preliminary behavioral and functional connectivity evidence from healthy participants that cerebellar neuromodulation may be useful for rehabilitation of aphasia.In Experiment 1, 76 healthy adults performed articulation and verbal fluency tasks before and after anodal, cathodal or sham transcranial direct current stimulation (tDCS) was applied over two cerebellar locations (anterior, right posterolateral). In Experiment 2, we examined whether anodal tDCS over the right posterolateral cerebellum modulated resting-state functional connectivity in language networks in 27 healthy adults.TDCS over the right posterolateral cerebellum significantly improved phonemic fluency. Cerebellar neuromodulation increased functional connectivity between the cerebellum and areas involved in the motor control of speech, and enhanced the correlations between left-hemisphere language and speech-motor regions.We provide proof-of-principle evidence that cerebellar neuromodulation improves verbal fluency and impacts resting-state connectivity in language circuits. These findings suggest that the cerebellum is a viable candidate for neuromodulation in people with aphasia.
    BibTeX:
    @article{TurkeltaubSwearsDMelloEtAl2016,
      author = {Turkeltaub, Peter E. and Swears, Mary K. and D'Mello, Anila M. and Stoodley, Catherine J.},
      title = {Cerebellar tDCS as a novel treatment for aphasia? Evidence from behavioral and resting-state functional connectivity data in healthy adults.},
      journal = {Restor Neurol Neurosci},
      school = {Center for Behavioral Neuroscience, American University, Washington D.C., USA.},
      year = {2016},
      url = {http://dx.doi.org/10.3233/RNN-150633},
      doi = {http://doi.org/10.3233/RNN-150633}
    }
    
    Turner, R.S., Chadwick, M., Horton, W.A., Simon, G.L., Jiang, X. & Esposito, G. An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition. 2016 Alzheimers Dement (Amst)
    Vol. 4, pp. 1-5School: Department of Radiology, Georgetown University, Washington, DC, USA. 
    DOI URL 
    Abstract: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is found in 3050% of individuals with HIV infection. To date, no HIV+ individual has been reported to have a positive amyloid PET scan. We report a 71-year-old HIV+ individual with HAND. Clinical and neuropsychologic evaluations confirmed a progressive mild dementia. A routine brain MRI was normal for age. [18F]Fluorodeoxyglucose-PET revealed mild hypermetabolism in bilateral basal ganglia and hypometabolism of bilateral parietal cortex including the posterior cingulate/precuneus. Resting state functional MRI revealed altered connectivity as found with individuals with mild AD. CSF examination revealed a low AΒ42/tau index but a low phospho-tau. An amyloid PET/CT with [18F]florbetaben revealed pronounced cortical radiotracer deposition. This case report suggests that progressive dementia in older HIV+ individuals may be due to HAND, AD, or both. HIV infection does not preclude CNS AΒ/amyloid deposition. Amyloid PET imaging may be of value in distinguishing HAND from AD pathologies.
    BibTeX:
    @article{TurnerChadwickHortonEtAl2016,
      author = {Turner, Raymond Scott and Chadwick, Melanie and Horton, Wesley A. and Simon, Gary L. and Jiang, Xiong and Esposito, Giuseppe},
      title = {An individual with human immunodeficiency virus, dementia, and central nervous system amyloid deposition.},
      journal = {Alzheimers Dement (Amst)},
      school = {Department of Radiology, Georgetown University, Washington, DC, USA.},
      year = {2016},
      volume = {4},
      pages = {1--5},
      url = {http://dx.doi.org/10.1016/j.dadm.2016.03.009},
      doi = {http://doi.org/10.1016/j.dadm.2016.03.009}
    }
    
    Washington, P.M. & Burns, M.P. The Effect of the APOE4 Gene on Accumulation of A$40 After Brain Injury Cannot Be Reversed by Increasing apoE4 Protein. 2016 J Neuropathol Exp NeurolSchool: From the Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC (PM, MB). mpb37@georgetown.edu.  DOI URL 
    Abstract: The apolipoprotein E (apoE) protein is involved in clearance of β-amyloid (AΒ) from the brain; and the APOE4 gene is associated with AΒ plaque formation in humans following traumatic brain injury (TBI). Here, we examined the association between apoE and AΒ40 after experimental TBI and the effects of APOE alleles on this relationship. We report a biphasic response of soluble apoE protein after TBI with an acute reduction at 1?day postinjury followed by an increase at 7 days postinjury. TBI-induced AΒ40 levels decreased as soluble apoE levels increased. In APOE4 mice there was a diminished apoE response to TBI that corresponded to prolonged accumulation of TBI-induced AΒ40 versus that in APOE3 mice. Amyloid precursor protein processing was similar in APOE3 and APOE4 mice suggesting that impaired clearance was responsible for the abnormal accumulation of AΒ40 in the latter. Treatment of APOE4 mice with bexarotene for 7 days increased apoE4 protein levels but was not sufficient to reduce TBI-induced AΒ40 Thus, rapid clearance of TBI-induced AΒ40 occurs in mice but these pathways are impaired in APOE4 carriers. These data may help explain the deposition of AΒ in APOE4 carriers and the increased incidence of brain AΒ plaques following TBI.
    BibTeX:
    @article{WashingtonBurns2016,
      author = {Washington, Patricia M. and Burns, Mark P.},
      title = {The Effect of the APOE4 Gene on Accumulation of A$40 After Brain Injury Cannot Be Reversed by Increasing apoE4 Protein.},
      journal = {J Neuropathol Exp Neurol},
      school = {From the Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC (PM, MB). mpb37@georgetown.edu.},
      year = {2016},
      url = {http://dx.doi.org/10.1093/jnen/nlw049},
      doi = {http://doi.org/10.1093/jnen/nlw049}
    }
    
    Washington, P.M., Villapol, S. & Burns, M.P. Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy? 2016 Exp Neurol
    Vol. 275 Pt 3, pp. 381-388School: Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: mpb37@georgetown.edu. 
    DOI URL 
    Abstract: Neuropathological studies of human traumatic brain injury (TBI) cases have described amyloid plaques acutely after a single severe TBI, and tau pathology after repeat mild TBI (mTBI). This has helped drive the hypothesis that a single moderate to severe TBI increases the risk of developing late-onset Alzheimer's disease (AD), while repeat mTBI increases the risk of developing chronic traumatic encephalopathy (CTE). In this review we critically assess this position-examining epidemiological and case control human studies, neuropathological evidence, and preclinical data. Epidemiological studies emphasize that TBI is associated with the increased risk of developing multiple types of dementia, not just AD-type dementia, and that TBI can also trigger other neurodegenerative conditions such as Parkinson's disease. Further, human post-mortem studies on both single TBI and repeat mTBI can show combinations of amyloid, tau, TDP-43, and Lewy body pathology indicating that the neuropathology of TBI is best described as a 'polypathology'. Preclinical studies confirm that multiple proteins associated with the development of neurodegenerative disease accumulate in the brain after TBI. The chronic sequelae of both single TBI and repeat mTBI share common neuropathological features and clinical symptoms of classically defined neurodegenerative disorders. However, while the spectrum of chronic cognitive and neurobehavioral disorders that occur following repeat mTBI is viewed as the symptoms of CTE, the spectrum of chronic cognitive and neurobehavioral symptoms that occur after a single TBI is considered to represent distinct neurodegenerative diseases such as AD. These data support the suggestion that the multiple manifestations of TBI-induced neurodegenerative disorders be classified together as traumatic encephalopathy or trauma-induced neurodegeneration, regardless of the nature or frequency of the precipitating TBI.
    BibTeX:
    @article{WashingtonVillapolBurns2016,
      author = {Washington, Patricia M. and Villapol, Sonia and Burns, Mark P.},
      title = {Polypathology and dementia after brain trauma: Does brain injury trigger distinct neurodegenerative diseases, or should they be classified together as traumatic encephalopathy?},
      journal = {Exp Neurol},
      school = {Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: mpb37@georgetown.edu.},
      year = {2016},
      volume = {275 Pt 3},
      pages = {381--388},
      url = {http://dx.doi.org/10.1016/j.expneurol.2015.06.015},
      doi = {http://doi.org/10.1016/j.expneurol.2015.06.015}
    }
    
    Wiener, M., Michaelis, K. & Thompson, J.C. Functional correlates of likelihood and prior representations in a virtual distance task. 2016 Hum Brain Mapp
    Vol. 37(9), pp. 3172-3187School: Department of Psychology, George Mason University, Fairfax, Virginia. 
    DOI URL 
    Abstract: Spatial navigation is an imperative cognitive function, in which individuals must interact with their environment in order to accurately reach a destination. Previous research has demonstrated that, when traveling a predetermined distance, humans must balance between noise in the measurement process and the prior history of traveled distances. This tradeoff has recently been formally described using Bayesian estimation; however, the neural correlates of Bayesian estimation during distance reproduction have yet to be investigated. Here, human subjects performed a virtual reality distance reproduction task during functional Magnetic Resonance Imaging (fMRI), in which they were required to reproduce various traveled distances in the absence of overt navigational cues. As previously demonstrated, subjects exhibited a central tendency effect, wherein reproduced distances gravitated to the mean of the stimulus set. fMRI activity during this task revealed distance-sensitive activity in a network of regions, including prefrontal and hippocampal regions. Using a computational index of central tendency, we found that activity in the retrosplenial cortex, a region highly implicated in spatial navigation, negatively covaried between subjects with the degree of central tendency observed; conversely, we found that activity in the anterior hippocampus/amygdala complex was positively correlated with the central tendency effect of gravitating to the average reproduced distance. These findings suggest dissociable roles for the retrosplenial cortex and hippocampal complex during distance reproduction, with both regions coordinating with the prefrontal cortex the influence of prior history of the environment with present experience. Hum Brain Mapp 37:3172-3187, 2016. © 2016 Wiley Periodicals, Inc.
    BibTeX:
    @article{WienerMichaelisThompson2016,
      author = {Wiener, Martin and Michaelis, Kelly and Thompson, James C.},
      title = {Functional correlates of likelihood and prior representations in a virtual distance task.},
      journal = {Hum Brain Mapp},
      school = {Department of Psychology, George Mason University, Fairfax, Virginia.},
      year = {2016},
      volume = {37},
      number = {9},
      pages = {3172--3187},
      url = {http://dx.doi.org/10.1002/hbm.23232},
      doi = {http://doi.org/10.1002/hbm.23232}
    }
    
    Winston, C.N., Noël, A., Neustadtl, A., Parsadanian, M., Barton, D.J., Chellappa, D., Wilkins, T.E., Alikhani, A.D., Zapple, D.N., Villapol, S., Planel, E. & Burns, M.P. Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma. 2016 Am J Pathol
    Vol. 186(3), pp. 552-567School: Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. Electronic address: mpb37@georgetown.edu. 
    DOI URL 
    Abstract: Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase ?-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact.
    BibTeX:
    @article{WinstonNoeelNeustadtlEtAl2016,
      author = {Winston, Charisse N. and Noël, Anastasia and Neustadtl, Aidan and Parsadanian, Maia and Barton, David J. and Chellappa, Deepa and Wilkins, Tiffany E. and Alikhani, Andrew D. and Zapple, David N. and Villapol, Sonia and Planel, Emmanuel and Burns, Mark P.},
      title = {Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.},
      journal = {Am J Pathol},
      school = {Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. Electronic address: mpb37@georgetown.edu.},
      year = {2016},
      volume = {186},
      number = {3},
      pages = {552--567},
      url = {http://dx.doi.org/10.1016/j.ajpath.2015.11.006},
      doi = {http://doi.org/10.1016/j.ajpath.2015.11.006}
    }
    
    Xing, S., Lacey, E.H., Skipper-Kallal, L.M., Jiang, X., Harris-Love, M.L., Zeng, J. & Turkeltaub, P.E. Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke. 2016 Brain
    Vol. 139(Pt 1), pp. 227-241School: 1 Department of Neurology, Georgetown University Medical Center, Washington, D.C., USA 3 Research Division, MedStar National Rehabilitation Hospital, Washington, D.C., USA turkeltp@georgetown.edu. 
    DOI URL 
    Abstract: The neural mechanisms underlying recovery of language after left hemisphere stroke remain elusive. Although older evidence suggested that right hemisphere language homologues compensate for damage in left hemisphere language areas, the current prevailing theory suggests that right hemisphere engagement is ineffective or even maladaptive. Using a novel combination of support vector regression-based lesion-symptom mapping and voxel-based morphometry, we aimed to determine whether local grey matter volume in the right hemisphere independently contributes to aphasia outcomes after chronic left hemisphere stroke. Thirty-two left hemisphere stroke survivors with aphasia underwent language assessment with the Western Aphasia Battery-Revised and tests of other cognitive domains. High-resolution T1-weighted images were obtained in aphasia patients and 30 demographically matched healthy controls. Support vector regression-based multivariate lesion-symptom mapping was used to identify critical language areas in the left hemisphere and then to quantify each stroke survivor's lesion burden in these areas. After controlling for these direct effects of the stroke on language, voxel-based morphometry was then used to determine whether local grey matter volumes in the right hemisphere explained additional variance in language outcomes. In brain areas in which grey matter volumes related to language outcomes, we then compared grey matter volumes in patients and healthy controls to assess post-stroke plasticity. Lesion-symptom mapping showed that specific left hemisphere regions related to different language abilities. After controlling for lesion burden in these areas, lesion size, and demographic factors, grey matter volumes in parts of the right temporoparietal cortex positively related to spontaneous speech, naming, and repetition scores. Examining whether domain general cognitive functions might explain these relationships, partial correlations demonstrated that grey matter volumes in these clusters related to verbal working memory capacity, but not other cognitive functions. Further, grey matter volumes in these areas were greater in stroke survivors than healthy control subjects. To confirm this result, 10 chronic left hemisphere stroke survivors with no history of aphasia were identified. Grey matter volumes in right temporoparietal clusters were greater in stroke survivors with aphasia compared to those without history of aphasia. These findings suggest that the grey matter structure of right hemisphere posterior dorsal stream language homologues independently contributes to language production abilities in chronic left hemisphere stroke, and that these areas may undergo hypertrophy after a stroke causing aphasia.
    BibTeX:
    @article{XingLaceySkipper-KallalEtAl2016,
      author = {Xing, Shihui and Lacey, Elizabeth H. and Skipper-Kallal, Laura M. and Jiang, Xiong and Harris-Love, Michelle L. and Zeng, Jinsheng and Turkeltaub, Peter E.},
      title = {Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke.},
      journal = {Brain},
      school = {1 Department of Neurology, Georgetown University Medical Center, Washington, D.C., USA 3 Research Division, MedStar National Rehabilitation Hospital, Washington, D.C., USA turkeltp@georgetown.edu.},
      year = {2016},
      volume = {139},
      number = {Pt 1},
      pages = {227--241},
      url = {http://dx.doi.org/10.1093/brain/awv323},
      doi = {http://doi.org/10.1093/brain/awv323}
    }
    
    Yu, W.-Q., Eom, Y.S., Shin, J.-A., Nair, D., Grzywacz, S.X.Z., Grzywacz, N.M., Craft, C.M. & Lee, E.-J. Reshaping the Cone-Mosaic in a Rat Model of Retinitis Pigmentosa: Modulatory Role of ZO-1 Expression in DL-Alpha-Aminoadipic Acid Reshaping. 2016 PLoS One
    Vol. 11(3), pp. e0151668School: Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America. 
    DOI URL 
    Abstract: In S334ter-line-3 rat model of Retinitis Pigmentosa (RP), rod cell death induces the rearrangement of cones into mosaics of rings while the fibrotic processes of M?ller cells remodel to fill the center of the rings. In contrast, previous work established that DL-alpha-aminoadipic-acid (AAA), a compound that transiently blocks M?ller cell metabolism, abolishes these highly structured cone rings. Simultaneously, adherens-junction associated protein, Zonula occludens-1 (ZO-1) expression forms in a network between the photoreceptor segments and M?ller cells processes. Thus, we hypothesized that AAA treatment alters the cone mosaic rings by disrupting the distal sealing formed by these fibrotic processes, either directly or indirectly, by down regulating the expression of ZO-1. Therefore, we examined these processes and ZO-1 expression at the outer retina after intravitreal injection of AAA and observed that AAA treatment transiently disrupts the distal glial sealing in RP retina, plus induces cones in rings to become more homogeneous. Moreover, ZO-1 expression is actively suppressed after 3 days of AAA treatment, which coincided with cone ring disruption. Similar modifications of glial sealing and cone distribution were observed after injection of siRNA to inhibit ZO-1 expression. These findings support our hypothesis and provide additional information about the critical role played by ZO-1 in glial sealing and shaping the ring mosaic in RP retina. These studies represent important advancements in the understanding of retinal degeneration's etiology and pathophysiology.
    BibTeX:
    @article{YuEomShinEtAl2016,
      author = {Yu, Wan-Qing and Eom, Yun Sung and Shin, Jung-A. and Nair, Divya and Grzywacz, Sara X Z. and Grzywacz, Norberto M. and Craft, Cheryl Mae and Lee, Eun-Jin},
      title = {Reshaping the Cone-Mosaic in a Rat Model of Retinitis Pigmentosa: Modulatory Role of ZO-1 Expression in DL-Alpha-Aminoadipic Acid Reshaping.},
      journal = {PLoS One},
      school = {Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.},
      year = {2016},
      volume = {11},
      number = {3},
      pages = {e0151668},
      url = {http://dx.doi.org/10.1371/journal.pone.0151668},
      doi = {http://doi.org/10.1371/journal.pone.0151668}
    }
    
    Bornkessel-Schlesewsky, I., Schlesewsky, M., Small, S.L. & Rauschecker, J.P. Neurobiological roots of language in primate audition: common computational properties. 2015 Trends Cogn Sci
    Vol. 19(3), pp. 142-150School: Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA; Institute for Advanced Study, Technische Universit?t M?nchen, Garching, Germany. 
    DOI URL 
    Abstract: Here, we present a new perspective on an old question: how does the
    neurobiology of human language relate to brain systems in nonhuman
    primates? We argue that higher-order language combinatorics, including
    sentence and discourse processing, can be situated in a unified,
    cross-species dorsal-ventral streams architecture for higher auditory
    processing, and that the functions of the dorsal and ventral streams
    in higher-order language processing can be grounded in their respective
    computational properties in primate audition. This view challenges
    an assumption, common in the cognitive sciences, that a nonhuman
    primate model forms an inherently inadequate basis for modeling higher-level
    language functions.
    BibTeX:
    @article{Bornkessel-Schlesewsky2015,
      author = {Bornkessel-Schlesewsky, Ina and Schlesewsky, Matthias and Small, Steven L. and Rauschecker, Josef P.},
      title = {Neurobiological roots of language in primate audition: common computational properties.},
      journal = {Trends Cogn Sci},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA; Institute for Advanced Study, Technische Universit?t M?nchen, Garching, Germany.},
      year = {2015},
      volume = {19},
      number = {3},
      pages = {142--150},
      url = {http://dx.doi.org/10.1016/j.tics.2014.12.008},
      doi = {http://doi.org/10.1016/j.tics.2014.12.008}
    }
    
    Campbell, L.A., Avdoshina, V., Day, C., Lim, S.T. & Mocchetti, I. Pharmacological induction of CCL5 in vivo prevents gp120-mediated neuronal injury. 2015 Neuropharmacology
    Vol. 92, pp. 98-107School: Laboratory of Preclinical Neurobiology, Georgetown University Medical Center, Washington, D.C. 20057, USA. Electronic address: moccheti@georgetown.edu. 
    DOI URL 
    Abstract: The human immunodeficiency virus (HIV) envelope protein gp120 promotes
    neuronal injury which is believed to cause HIV-associated neurocognitive
    disorders. Therefore, blocking the neurotoxic effect of gp120 may
    lead to alternative strategies to reduce the neurotoxic effect of
    HIV. In vitro, the neurotoxic effect of M-tropic gp120BaL is reduced
    by the chemokine CCL5, the natural ligand of CCR5 receptors. To determine
    whether CCL5 reduces the toxic effect of gp120BaL in vivo, animals
    were intrastriatally injected with lentiviral vectors overexpressing
    CCL5 prior to an intrastriatal injection of gp120BaL (400 ng). Neuronal
    injury was determined by silver staining, cleaved caspase-3 and TUNEL.
    Overexpression of CCL5 decreased gp120-mediated neuronal injury.
    CCL5 expression can be up-regulated by chronic morphine. Therefore,
    we examined whether morphine reduces the neurotoxic effect of gp120BaL.
    Rats stereotaxically injected with gp120BaL into the striatum received
    saline or chronic morphine for five days (10 mg/kg escalating to
    30 mg/kg twice a day). Morphine-treated rats showed a decrease in
    all markers used to determine neuronal degeneration compared to saline-treated
    rats. The neuroprotective effect of morphine was significantly attenuated
    by expressing CCL5 shRNA. Our results suggest that compounds that
    increase the endogenous production of CCL5 may be used to reduce
    the pathogenesis of HIV-associated neurocognitive disorders.
    BibTeX:
    @article{Campbell2015,
      author = {Campbell, Lee A. and Avdoshina, Valeriya and Day, Chris and Lim, Seung T. and Mocchetti, Italo},
      title = {Pharmacological induction of CCL5 in vivo prevents gp120-mediated neuronal injury.},
      journal = {Neuropharmacology},
      school = { Laboratory of Preclinical Neurobiology, Georgetown University Medical Center, Washington, D.C. 20057, USA. Electronic address: moccheti@georgetown.edu.},
      year = {2015},
      volume = {92},
      pages = {98--107},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2015.01.009},
      doi = {http://doi.org/10.1016/j.neuropharm.2015.01.009}
    }
    
    Chamberlain, K.A., Nanescu, S.E., Psachoulia, K. & Huang, J.K. Oligodendrocyte regeneration: Its significance in myelin replacement and neuroprotection in multiple sclerosis. 2015 NeuropharmacologySchool: Department of Biology, Georgetown University, Washington, D.C., USA; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, D.C., USA. Electronic address: jh1659@georgetown.edu.  DOI URL 
    Abstract: Oligodendrocytes readily regenerate and replace myelin membranes around axons in the adult mammalian central nervous system (CNS) following injury. The ability to regenerate oligodendrocytes depends on the availability of neural progenitors called oligodendrocyte precursor cells (OPCs) in the adult CNS that respond to injury-associated signals to induce OPC expansion followed by oligodendrocyte differentiation, axonal contact and myelin regeneration (remyelination). Remyelination ensures the maintenance of axonal conduction, and the oligodendrocytes themselves provide metabolic factors that are necessary to maintain neuronal integrity. Recent advances in oligodendrocyte regeneration research are beginning to shed light on critical intrinsic signals, as well as extrinsic, environmental factors that regulate the distinct steps of oligodendrocyte lineage progression and myelin replacement under CNS injury. These studies may offer novel pharmacological targets for regenerative medicine in inflammatory demyelinating disorders in the CNS such as multiple sclerosis.
    BibTeX:
    @article{ChamberlainNanescuPsachouliaEtAl2015,
      author = {Chamberlain, Kelly A. and Nanescu, Sonia E. and Psachoulia, Konstantina and Huang, Jeffrey K.},
      title = {Oligodendrocyte regeneration: Its significance in myelin replacement and neuroprotection in multiple sclerosis.},
      journal = {Neuropharmacology},
      school = {Department of Biology, Georgetown University, Washington, D.C., USA; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, D.C., USA. Electronic address: jh1659@georgetown.edu.},
      year = {2015},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2015.10.010},
      doi = {http://doi.org/10.1016/j.neuropharm.2015.10.010}
    }
    
    Conant, K., Allen, M. & Lim, S.T. Activity dependent CAM cleavage and neurotransmission. 2015 Front Cell Neurosci
    Vol. 9, pp. 305School: Department of Neuroscience and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: Spatially localized proteolysis represents an elegant means by which neuronal activity dependent changes in synaptic structure, and thus experience dependent learning and memory, can be achieved. In vitro and in vivo studies suggest that matrix metalloproteinase and adamalysin activity is concentrated at the cell surface, and emerging evidence suggests that increased peri-synaptic expression, release and/or activation of these proteinases occurs with enhanced excitatory neurotransmission. Synaptically expressed cell adhesion molecules (CAMs) could therefore represent important targets for neuronal activity-dependent proteolysis. Several CAM subtypes are expressed at the synapse, and their cleavage can influence the efficacy of synaptic transmission through a variety of non-mutually exclusive mechanisms. In the following review, we discuss mechanisms that regulate neuronal activity-dependent synaptic CAM shedding, including those that may be calcium dependent. We also highlight CAM targets of activity-dependent proteolysis including neuroligin and intercellular adhesion molecule-5 (ICAM-5). We include discussion focused on potential consequences of synaptic CAM shedding, with an emphasis on interactions between soluble CAM cleavage products and specific pre- and post-synaptic receptors.
    BibTeX:
    @article{ConantAllenLim2015,
      author = {Conant, Katherine and Allen, Megan and Lim, Seung T.},
      title = {Activity dependent CAM cleavage and neurotransmission.},
      journal = {Front Cell Neurosci},
      school = {Department of Neuroscience and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA.},
      year = {2015},
      volume = {9},
      pages = {305},
      url = {http://dx.doi.org/10.3389/fncel.2015.00305},
      doi = {http://doi.org/10.3389/fncel.2015.00305}
    }
    
    Cox, P.H. & Riesenhuber, M. There Is a "U" in Clutter: Evidence for Robust Sparse Codes Underlying Clutter Tolerance in Human Vision. 2015 J Neurosci
    Vol. 35(42), pp. 14148-14159School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007 mr287@georgetown.edu. 
    DOI URL 
    Abstract: The ability to recognize objects in clutter is crucial for human vision, yet the underlying neural computations remain poorly understood. Previous single-unit electrophysiology recordings in inferotemporal cortex in monkeys and fMRI studies of object-selective cortex in humans have shown that the responses to pairs of objects can sometimes be well described as a weighted average of the responses to the constituent objects. Yet, from a computational standpoint, it is not clear how the challenge of object recognition in clutter can be solved if downstream areas must disentangle the identity of an unknown number of individual objects from the confounded average neuronal responses. An alternative idea is that recognition is based on a subpopulation of neurons that are robust to clutter, i.e., that do not show response averaging, but rather robust object-selective responses in the presence of clutter. Here we show that simulations using the HMAX model of object recognition in cortex can fit the aforementioned single-unit and fMRI data, showing that the averaging-like responses can be understood as the result of responses of object-selective neurons to suboptimal stimuli. Moreover, the model shows how object recognition can be achieved by a sparse readout of neurons whose selectivity is robust to clutter. Finally, the model provides a novel prediction about human object recognition performance, namely, that target recognition ability should show a U-shaped dependency on the similarity of simultaneously presented clutter objects. This prediction is confirmed experimentally, supporting a simple, unifying model of how the brain performs object recognition in clutter.The neural mechanisms underlying object recognition in cluttered scenes (i.e., containing more than one object) remain poorly understood. Studies have suggested that neural responses to multiple objects correspond to an average of the responses to the constituent objects. Yet, it is unclear how the identities of an unknown number of objects could be disentangled from a confounded average response. Here, we use a popular computational biological vision model to show that averaging-like responses can result from responses of clutter-tolerant neurons to suboptimal stimuli. The model also provides a novel prediction, that human detection ability should show a U-shaped dependency on target-clutter similarity, which is confirmed experimentally, supporting a simple, unifying account of how the brain performs object recognition in clutter.
    BibTeX:
    @article{CoxRiesenhuber2015,
      author = {Cox, Patrick H. and Riesenhuber, Maximilian},
      title = {There Is a "U" in Clutter: Evidence for Robust Sparse Codes Underlying Clutter Tolerance in Human Vision.},
      journal = {J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007 mr287@georgetown.edu.},
      year = {2015},
      volume = {35},
      number = {42},
      pages = {14148--14159},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.1211-15.2015},
      doi = {http://doi.org/10.1523/JNEUROSCI.1211-15.2015}
    }
    
    Daniele, S.G., Béraud, D., Davenport, C., Cheng, K., Yin, H. & Maguire-Zeiss, K.A. Activation of MyD88-dependent TLR1/2 signaling by misfolded α-synuclein, a protein linked to neurodegenerative disorders. 2015 Sci Signal
    Vol. 8(376), pp. ra45School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. km445@georgetown.edu hubert.yin@colorado.edu. 
    DOI URL 
    Abstract: Synucleinopathies, such as Parkinson's disease and diffuse Lewy body disease, are progressive neurodegenerative disorders characterized by selective neuronal death, abnormal accumulation of misfolded α-synuclein, and sustained microglial activation. In addition to inducing neuronal toxicity, higher-ordered oligomeric α-synuclein causes proinflammatory responses in the brain parenchyma by triggering microglial activation, which may exacerbate pathogenic processes by establishing a chronic neuroinflammatory milieu. We found that higher-ordered oligomeric α-synuclein induced a proinflammatory microglial phenotype by directly engaging the heterodimer TLR1/2 (Toll-like receptor 1 and 2) at the cell membrane, leading to the nuclear translocation of NF-?B (nuclear factor ?B) and the increased production of the proinflammatory cytokines TNF-? (tumor necrosis factor-?) and IL-1? (interleukin-1?) in a MyD88-dependent manner. Blocking signaling through the TLR1/2 heterodimer with the small-molecule inhibitor CU-CPT22 reduced the nuclear translocation of NF-?B and secretion of TNF-? from cultured primary mouse microglia. Candesartan cilexetil, a drug approved for treating hypertension and that inhibits the expression of TLR2, reversed the activated proinflammatory phenotype of primary microglia exposed to oligomeric α-synuclein, supporting the possibility of repurposing this drug for synucleinopathies.
    BibTeX:
    @article{DanieleBeraudDavenportEtAl2015,
      author = {Daniele, Stefano G. and Béraud, Dawn and Davenport, Connor and Cheng, Kui and Yin, Hang and Maguire-Zeiss, Kathleen A.},
      title = {Activation of MyD88-dependent TLR1/2 signaling by misfolded $-synuclein, a protein linked to neurodegenerative disorders.},
      journal = {Sci Signal},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. km445@georgetown.edu hubert.yin@colorado.edu.},
      year = {2015},
      volume = {8},
      number = {376},
      pages = {ra45},
      url = {http://dx.doi.org/10.1126/scisignal.2005965},
      doi = {http://doi.org/10.1126/scisignal.2005965}
    }
    
    DeWitt, I. & Rauschecker, J.P. Convergent evidence for the causal involvement of anterior superior temporal gyrus in auditory single-word comprehension. 2015 CortexSchool: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: rauschej@georgetown.edu.  DOI URL 
    BibTeX:
    @article{DeWittRauschecker2015,
      author = {DeWitt, Iain and Rauschecker, Josef P.},
      title = {Convergent evidence for the causal involvement of anterior superior temporal gyrus in auditory single-word comprehension.},
      journal = {Cortex},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: rauschej@georgetown.edu.},
      year = {2015},
      url = {http://dx.doi.org/10.1016/j.cortex.2015.08.016},
      doi = {http://doi.org/10.1016/j.cortex.2015.08.016}
    }
    
    DiBattista, A.M., Dumanis, S.B., Song, J.M., Bu, G., Weeber, E., Rebeck, G.W. & Hoe, H.-S. Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner. 2015 Biochim Biophys Acta
    Vol. 1853(5), pp. 904-917School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr. 
    DOI URL 
    Abstract: Very Low Density Lipoprotein Receptor (VLDLR) is an apolipoprotein E receptor involved in synaptic plasticity, learning, and memory. However, it is unknown how VLDLR can regulate synaptic and cognitive function. In the present study, we found that VLDLR is present at the synapse both pre- and post-synaptically. Overexpression of VLDLR significantly increases, while knockdown of VLDLR decreases, dendritic spine number in primary hippocampal cultures. Additionally, knockdown of VLDLR significantly decreases synaptophysin puncta number while differentially regulating cell surface and total levels of glutamate receptor subunits. To identify the mechanism by which VLDLR induces these synaptic effects, we investigated whether VLDLR affects dendritic spine formation through the Ras signaling pathway, which is involved in spinogenesis and neurodegeneration. Interestingly, we found that VLDLR interacts with RasGRF1, a Ras effector, and knockdown of RasGRF1 blocks the effect of VLDLR on spinogenesis. Moreover, we found that VLDLR did not rescue the deficits induced by the absence of Ras signaling proteins CaMKII? or CaMKII?. Taken together, our results suggest that VLDLR requires RasGRF1/CaMKII to alter dendritic spine formation.
    BibTeX:
    @article{DiBattistaDumanisSongEtAl2015,
      author = {DiBattista, Amanda Marie and Dumanis, Sonya B. and Song, Jung Min and Bu, Guojun and Weeber, Edwin and Rebeck, G William and Hoe, Hyang-Sook},
      title = {Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner.},
      journal = {Biochim Biophys Acta},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr.},
      year = {2015},
      volume = {1853},
      number = {5},
      pages = {904--917},
      url = {http://dx.doi.org/10.1016/j.bbamcr.2015.01.015},
      doi = {http://doi.org/10.1016/j.bbamcr.2015.01.015}
    }
    
    DiBattista, A.M., Dumanis, S.B., Song, J.M., Bu, G., Weeber, E., William Rebeck, G. & Hoe, H.-S. Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner. 2015 Biochim Biophys Acta
    Vol. 1853(5), pp. 904-917School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr. 
    DOI URL 
    Abstract: Very Low Density Lipoprotein Receptor (VLDLR) is an apolipoprotein
    E receptor involved in synaptic plasticity, learning, and memory.
    However, it is unknown how VLDLR can regulate synaptic and cognitive
    function. In the present study, we found that VLDLR is present at
    the synapse both pre- and post-synaptically. Overexpression of VLDLR
    significantly increases, while knockdown of VLDLR decreases, dendritic
    spine number in primary hippocampal cultures. Additionally, knockdown
    of VLDLR significantly decreases synaptophysin puncta number while
    differentially regulating cell surface and total levels of glutamate
    receptor subunits. To identify the mechanism by which VLDLR induces
    these synaptic effects, we investigated whether VLDLR affects dendritic
    spine formation through the Ras signaling pathway, which is involved
    in spinogenesis and neurodegeneration. Interestingly, we found that
    VLDLR interacts with RasGRF1, a Ras effector, and knockdown of RasGRF1
    blocks the effect of VLDLR on spinogenesis. Moreover, we found that
    VLDLR did not rescue the deficits induced by the absence of Ras signaling
    proteins CaMKII? or CaMKII?. Taken together, our results suggest
    that VLDLR requires RasGRF1/CaMKII to alter dendritic spine formation.
    BibTeX:
    @article{DiBattista2015,
      author = {DiBattista, Amanda Marie and Dumanis, Sonya B. and Song, Jung Min and Bu, Guojun and Weeber, Edwin and William Rebeck, G. and Hoe, Hyang-Sook},
      title = {Very low density lipoprotein receptor regulates dendritic spine formation in a RasGRF1/CaMKII dependent manner.},
      journal = {Biochim Biophys Acta},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr.},
      year = {2015},
      volume = {1853},
      number = {5},
      pages = {904--917},
      url = {http://dx.doi.org/10.1016/j.bbamcr.2015.01.015},
      doi = {http://doi.org/10.1016/j.bbamcr.2015.01.015}
    }
    
    Glezer, L.S., Kim, J., Rule, J., Jiang, X. & Riesenhuber, M. Adding Words to the Brain's Visual Dictionary: Novel Word Learning Selectively Sharpens Orthographic Representations in the VWFA. 2015 J Neurosci
    Vol. 35(12), pp. 4965-4972School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20007 mr287@georgetown.edu. 
    DOI URL 
    Abstract: The nature of orthographic representations in the human brain is still
    subject of much debate. Recent reports have claimed that the visual
    word form area (VWFA) in left occipitotemporal cortex contains an
    orthographic lexicon based on neuronal representations highly selective
    for individual written real words (RWs). This theory predicts that
    learning novel words should selectively increase neural specificity
    for these words in the VWFA. We trained subjects to recognize novel
    pseudowords (PWs) and used fMRI rapid adaptation to compare neural
    selectivity with RWs, untrained PWs (UTPWs), and trained PWs (TPWs).
    Before training, PWs elicited broadly tuned responses, whereas responses
    to RWs indicated tight tuning. After training, TPW responses resembled
    those of RWs, whereas UTPWs continued to show broad tuning. This
    change in selectivity was specific to the VWFA. Therefore, word learning
    appears to selectively increase neuronal specificity for the new
    words in the VWFA, thereby adding these words to the brain's visual
    dictionary.
    BibTeX:
    @article{Glezer2015,
      author = {Glezer, Laurie S. and Kim, Judy and Rule, Josh and Jiang, Xiong and Riesenhuber, Maximilian},
      title = {Adding Words to the Brain's Visual Dictionary: Novel Word Learning Selectively Sharpens Orthographic Representations in the VWFA.},
      journal = {J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20007 mr287@georgetown.edu.},
      year = {2015},
      volume = {35},
      number = {12},
      pages = {4965--4972},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.4031-14.2015},
      doi = {http://doi.org/10.1523/JNEUROSCI.4031-14.2015}
    }
    
    Harrington, R.M., Chan, E., Turkeltaub, P.E., Dromerick, A.W. & Harris-Love, M.L. Simple Partial Status Epilepticus One-day Post Single-pulse TMS to the Affected Hemisphere in a Participant With Chronic Stroke. 2015 Brain StimulSchool: Assistant Professor of Neurology, Georgetown University Medical Center, USA; Director of MOTR Lab, National Rehabilitation Hospital, USA.  DOI URL 
    BibTeX:
    @article{Harrington2015,
      author = {Harrington, Rachael M. and Chan, Evan and Turkeltaub, Peter E. and Dromerick, Alexander W. and Harris-Love, Michelle L.},
      title = {Simple Partial Status Epilepticus One-day Post Single-pulse TMS to the Affected Hemisphere in a Participant With Chronic Stroke.},
      journal = {Brain Stimul},
      school = {Assistant Professor of Neurology, Georgetown University Medical Center, USA; Director of MOTR Lab, National Rehabilitation Hospital, USA.},
      year = {2015},
      url = {http://dx.doi.org/10.1016/j.brs.2015.01.417},
      doi = {http://doi.org/10.1016/j.brs.2015.01.417}
    }
    
    Hathaway, H.A., Pshenichkin, S., Grajkowska, E., Gelb, T., Emery, A.C., Wolfe, B.B. & Wroblewski, J.T. Pharmacological characterization of mGlu1 receptors in cerebellar granule cells reveals biased agonism. 2015 Neuropharmacology
    Vol. 93, pp. 199-208School: Department of Pharmacology and Physiology, Georgetown University, Washington, D.C. 20057, USA. 
    DOI URL 
    BibTeX:
    @article{Hathaway2015,
      author = {Hathaway, Hannah A. and Pshenichkin, Sergey and Grajkowska, Ewa and Gelb, Tara and Emery, Andrew C. and Wolfe, Barry B. and Wroblewski, Jarda T.},
      title = {Pharmacological characterization of mGlu1 receptors in cerebellar granule cells reveals biased agonism.},
      journal = {Neuropharmacology},
      school = {Department of Pharmacology and Physiology, Georgetown University, Washington, D.C. 20057, USA.},
      year = {2015},
      volume = {93},
      pages = {199--208},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2015.02.007},
      doi = {http://doi.org/10.1016/j.neuropharm.2015.02.007}
    }
    
    Hung, C.P., Cui, D., Chen, Y.-P., Lin, C.-P. & Levine, M.R. Corrigendum: Correlated activity supports efficient cortical processing. 2015 Front Comput Neurosci
    Vol. 9, pp. 25School: Department of Neuroscience, Georgetown University Washington, DC, USA. 
    DOI URL 
    Abstract: [This corrects the article on p. 171 in vol. 8, PMID: 25610392.].
    BibTeX:
    @article{Hung2015,
      author = {Hung, Chou P. and Cui, Ding and Chen, Yueh-Peng and Lin, Chia-Pei and Levine, Matthew R.},
      title = {Corrigendum: Correlated activity supports efficient cortical processing.},
      journal = {Front Comput Neurosci},
      school = {Department of Neuroscience, Georgetown University Washington, DC, USA.},
      year = {2015},
      volume = {9},
      pages = {25},
      url = {http://dx.doi.org/10.3389/fncom.2015.00025},
      doi = {http://doi.org/10.3389/fncom.2015.00025}
    }
    
    Lacey, E.H., Jiang, X., Friedman, R.B., Snider, S.F., Parra, L.C., Huang, Y. & Turkeltaub, P.E. Transcranial direct current stimulation for pure alexia: effects on brain and behavior. 2015 Brain Stimul
    Vol. 8(2), pp. 305-307School: Department of Neurology, Georgetown University, USA; MedStar National Rehabilitation Hospital, USA. 
    DOI URL 
    BibTeX:
    @article{Lacey2015,
      author = {Lacey, E. H. and Jiang, X. and Friedman, R. B. and Snider, S. F. and Parra, L. C. and Huang, Y. and Turkeltaub, P. E.},
      title = {Transcranial direct current stimulation for pure alexia: effects on brain and behavior.},
      journal = {Brain Stimul},
      school = {Department of Neurology, Georgetown University, USA; MedStar National Rehabilitation Hospital, USA.},
      year = {2015},
      volume = {8},
      number = {2},
      pages = {305--307},
      url = {http://dx.doi.org/10.1016/j.brs.2014.10.019},
      doi = {http://doi.org/10.1016/j.brs.2014.10.019}
    }
    
    Leaver, A.M., Seydell-Greenwald, A. & Rauschecker, J.P. Auditory-limbic interactions in chronic tinnitus: Challenges for neuroimaging research. 2015 Hear ResSchool: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA; Institute for Advanced Study, TUM, Munich, Germany. Electronic address: rauschej@georgetown.edu.  DOI URL 
    Abstract: Tinnitus is a widespread auditory disorder affecting approximately 10-15% of the population, often with debilitating consequences. Although tinnitus commonly begins with damage to the auditory system due to loud-noise exposure, aging, or other etiologies, the exact neurophysiological basis of chronic tinnitus remains unknown. Many researchers point to a central auditory origin of tinnitus; however, a growing body of evidence also implicates other brain regions, including the limbic system. Correspondingly, we and others have proposed models of tinnitus in which the limbic and auditory systems both play critical roles and interact with one another. Specifically, we argue that damage to the auditory system generates an initial tinnitus signal, consistent with previous research. In our model, this "transient" tinnitus is suppressed when a limbic frontostriatal network, comprised of ventromedial prefrontal cortex and ventral striatum, successfully modulates thalamocortical transmission in the auditory system. Thus, in chronic tinnitus, limbic-system damage and resulting inefficiency of auditory-limbic interactions prevents proper compensation of the tinnitus signal. Neuroimaging studies utilizing connectivity methods like resting-state fMRI and diffusion MRI continue to uncover tinnitus-related anomalies throughout auditory, limbic, and other brain systems. However, directly assessing interactions between these brain regions and networks has proved to be more challenging. Here, we review existing empirical support for models of tinnitus stressing a critical role for involvement of "non-auditory" structures in tinnitus pathophysiology, and discuss the possible impact of newly refined connectivity techniques from neuroimaging on tinnitus research.
    BibTeX:
    @article{LeaverSeydell-GreenwaldRauschecker2015,
      author = {Leaver, Amber M. and Seydell-Greenwald, Anna and Rauschecker, Josef P.},
      title = {Auditory-limbic interactions in chronic tinnitus: Challenges for neuroimaging research.},
      journal = {Hear Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA; Institute for Advanced Study, TUM, Munich, Germany. Electronic address: rauschej@georgetown.edu.},
      year = {2015},
      url = {http://dx.doi.org/10.1016/j.heares.2015.08.005},
      doi = {http://doi.org/10.1016/j.heares.2015.08.005}
    }
    
    Lum, J.A.G., Ullman, M.T. & Conti-Ramsden, G. Verbal declarative memory impairments in specific language impairment are related to working memory deficits. 2015 Brain Lang
    Vol. 142, pp. 76-85School: School of Psychological Sciences, The University of Manchester, United Kingdom. 
    DOI URL 
    Abstract: This study examined verbal declarative memory functioning in SLI and
    its relationship to working memory. Encoding, recall, and recognition
    of verbal information was examined in children with SLI who had below
    average working memory (SLILow WM), children with SLI who had average
    working memory (SLIAvg. WM) and, a group of non-language impaired
    children with average working memory (TDAvg. WM). The SLILow WM group
    was significantly worse than both the SLIAvg. WM and TDAvg. WM groups
    at encoding verbal information and at retrieving verbal information
    following a delay. In contrast, the SLIAvg. WM group showed no verbal
    declarative memory deficits. The study demonstrates that verbal declarative
    memory deficits in SLI only occur when verbal working memory is impaired.
    Thus SLI declarative memory is largely intact and deficits are likely
    to be related to working memory impairments.
    BibTeX:
    @article{Lum2015,
      author = {Lum, Jarrad A G. and Ullman, Michael T. and Conti-Ramsden, Gina},
      title = {Verbal declarative memory impairments in specific language impairment are related to working memory deficits.},
      journal = {Brain Lang},
      school = {School of Psychological Sciences, The University of Manchester, United Kingdom.},
      year = {2015},
      volume = {142},
      pages = {76--85},
      url = {http://dx.doi.org/10.1016/j.bandl.2015.01.008},
      doi = {http://doi.org/10.1016/j.bandl.2015.01.008}
    }
    
    N'Gouemo, P., Akinfiresoye, L.R., Allard, J.S. & Lovinger, D.M. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus. 2015 Int J NeuropsychopharmacolSchool: Biophysics, Washington DC (Dr Allard); Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (Dr Lovinger).  DOI URL 
    Abstract: We previously reported increased current density through L-type voltage-gated
    Ca(2+) (CaV1) channels in inferior colliculus (IC) neurons during
    alcohol withdrawal. However, the molecular correlate of this increased
    CaV1 current is currently unknown.Rats received three daily doses
    of ethanol every 8 hours for 4 consecutive days; control rats received
    vehicle. The IC was dissected at various time intervals following
    alcohol withdrawal, and the mRNA and protein levels of the CaV1.3
    and CaV1.2 ?1 subunits were measured. In separate experiments, rats
    were tested for their susceptibility to alcohol withdrawal-induced
    seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal.In the
    alcohol-treated group, AWS were observed 24 hours after withdrawal;
    no seizures were observed at 3 or 48 hours. No seizures were observed
    at any time in the control-treated rats. Compared to control-treated
    rats, the mRNA level of the CaV1.3 ?1 subunit was increased 1.4-fold,
    1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast,
    the mRNA level of the CaV1.2 ?1 subunit increased 1.5-fold and 1.4-fold
    at 24 and 48 hours, respectively. At 24 hours, Western blot analyses
    revealed that the levels of the CaV1.3 and CaV1.2 ?1 subunits increased
    by 52% and 32 respectively, 24 hours after alcohol withdrawal.
    In contrast, the CaV1.2 and CaV1.3 ?1 subunits were not altered at
    either 3 or 48 hours during alcohol withdrawal.Expression of the
    CaV1.3 ?1 subunit increased in parallel with AWS development, suggesting
    that altered L-type CaV1.3 channel expression is an important feature
    of AWS pathogenesis.
    BibTeX:
    @article{NGouemo2015,
      author = {N'Gouemo, Prosper and Akinfiresoye, Luli R. and Allard, Joanne S. and Lovinger, David M.},
      title = {Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus.},
      journal = {Int J Neuropsychopharmacol},
      school = { Biophysics, Washington DC (Dr Allard); Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD (Dr Lovinger).},
      year = {2015},
      url = {http://dx.doi.org/10.1093/ijnp/pyu123},
      doi = {http://doi.org/10.1093/ijnp/pyu123}
    }
    
    Nemeth, D., Janacsek, K., Turi, Z., Lukacs, A., Peckham, D., Szanka, S., Gazso, D., Lovassy, N. & Ullman, M.T. The production of nominal and verbal inflection in an agglutinative language: evidence from hungarian. 2015 PLoS One
    Vol. 10(3), pp. e0119003School: Brain and Language Lab, Department of Neuroscience, Georgetown University, Washington, DC, United States of America. 
    DOI URL 
    Abstract: The contrast between regular and irregular inflectional morphology
    has been useful in investigating the functional and neural architecture
    of language. However, most studies have examined the regular/irregular
    distinction in non-agglutinative Indo-European languages (primarily
    English) with relatively simple morphology. Additionally, the majority
    of research has focused on verbal rather than nominal inflectional
    morphology. The present study attempts to address these gaps by introducing
    both plural and past tense production tasks in Hungarian, an agglutinative
    non-Indo-European language with complex morphology. Here we report
    results on these tasks from healthy Hungarian native-speaking adults,
    in whom we examine regular and irregular nominal and verbal inflection
    in a within-subjects design. Regular and irregular nouns and verbs
    were stem on frequency, word length, and phonological structure,
    and both accuracy and response times were acquired. The results revealed
    that the regular/irregular contrast yields similar patterns in Hungarian,
    for both nominal and verbal inflection, as in previous studies of
    non-agglutinative Indo-European languages: the production of irregular
    inflected forms was both less accurate and slower than of regular
    forms, both for plural and past-tense inflection. The results replicate
    and extend previous findings to an agglutinative language with complex
    morphology. Together with previous studies, the evidence suggests
    that the regular/irregular distinction yields a basic behavioral
    pattern that holds across language families and linguistic typologies.
    Finally, the study sets the stage for further research examining
    the neurocognitive substrates of regular and irregular morphology
    in an agglutinative non-Indo-European language.
    BibTeX:
    @article{Nemeth2015,
      author = {Nemeth, Dezso and Janacsek, Karolina and Turi, Zsolt and Lukacs, Agnes and Peckham, Don and Szanka, Szilvia and Gazso, Dorottya and Lovassy, Noemi and Ullman, Michael T.},
      title = {The production of nominal and verbal inflection in an agglutinative language: evidence from hungarian.},
      journal = {PLoS One},
      school = {Brain and Language Lab, Department of Neuroscience, Georgetown University, Washington, DC, United States of America.},
      year = {2015},
      volume = {10},
      number = {3},
      pages = {e0119003},
      url = {http://dx.doi.org/10.1371/journal.pone.0119003},
      doi = {http://doi.org/10.1371/journal.pone.0119003}
    }
    
    Niedringhaus, M., Chen, X. & Dzakpasu, R. Long-Term Dynamical Constraints on Pharmacologically Evoked Potentiation Imply Activity Conservation within In Vitro Hippocampal Networks. 2015 PLoS One
    Vol. 10(6), pp. e0129324School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America; Department of Physics, Georgetown University, Washington, District of Columbia, United States of America; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, District of Columbia, United States of America. 
    DOI URL 
    Abstract: This paper describes a long-term study of network dynamics from in vitro, cultured hippocampal neurons after a pharmacological induction of synaptic potentiation. We plate a suspension of hippocampal neurons on an array of extracellular electrodes and record electrical activity in the absence of the drugs several days after treatment. While previous studies have reported on potentiation lasting up to a few hours after treatment, to the best of our knowledge, this is the first report to characterize the network effects of a potentiating mechanism several days after treatment. Using this reduced, two-dimensional in vitro network of hippocampal neurons, we show that the effects of potentiation are persistent over time but are modulated under a conservation of spike principle. We suggest that this conservation principle might be mediated by the appearance of a resonant inter-spike interval that prevents the network from advancing towards a state of hyperexcitability.
    BibTeX:
    @article{NiedringhausChenDzakpasu2015,
      author = {Niedringhaus, Mark and Chen, Xin and Dzakpasu, Rhonda},
      title = {Long-Term Dynamical Constraints on Pharmacologically Evoked Potentiation Imply Activity Conservation within In Vitro Hippocampal Networks.},
      journal = {PLoS One},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America; Department of Physics, Georgetown University, Washington, District of Columbia, United States of America; Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, District of Columbia, United States of America.},
      year = {2015},
      volume = {10},
      number = {6},
      pages = {e0129324},
      url = {http://dx.doi.org/10.1371/journal.pone.0129324},
      doi = {http://doi.org/10.1371/journal.pone.0129324}
    }
    
    Ortiz-Rios, M., Ku?mierek, P., DeWitt, I., Archakov, D., Azevedo, F.A.C., Sams, M., J??skel?inen, I.P., Keliris, G.A. & Rauschecker, J.P. Functional MRI of the vocalization-processing network in the macaque brain. 2015 Front Neurosci
    Vol. 9, pp. 113School: Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA ; Brain and Mind Laboratory, Department of Neuroscience and Biomedical Engineering, Aalto University School of Science Aalto, Finland ; Institute for Advanced Study and Department of Neurology, Klinikum Rechts der Isar, Technische Universit?t M?nchen M?nchen, Germany. 
    DOI URL 
    Abstract: Using functional magnetic resonance imaging in awake behaving monkeys
    we investigated how species-specific vocalizations are represented
    in auditory and auditory-related regions of the macaque brain. We
    found clusters of active voxels along the ascending auditory pathway
    that responded to various types of complex sounds: inferior colliculus
    (IC), medial geniculate nucleus (MGN), auditory core, belt, and parabelt
    cortex, and other parts of the superior temporal gyrus (STG) and
    sulcus (STS). Regions sensitive to monkey calls were most prevalent
    in the anterior STG, but some clusters were also found in frontal
    and parietal cortex on the basis of comparisons between responses
    to calls and environmental sounds. Surprisingly, we found that spectrotemporal
    control sounds derived from the monkey calls ("scrambled calls")
    also activated the parietal and frontal regions. Taken together,
    our results demonstrate that species-specific vocalizations in rhesus
    monkeys activate preferentially the auditory ventral stream, and
    in particular areas of the antero-lateral belt and parabelt.
    BibTeX:
    @article{Ortiz-Rios2015,
      author = {Ortiz-Rios, Michael and Ku?mierek, Pawe? and DeWitt, Iain and Archakov, Denis and Azevedo, Frederico A C. and Sams, Mikko and J??skel?inen, Iiro P. and Keliris, Georgios A. and Rauschecker, Josef P.},
      title = {Functional MRI of the vocalization-processing network in the macaque brain.},
      journal = {Front Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA ; Brain and Mind Laboratory, Department of Neuroscience and Biomedical Engineering, Aalto University School of Science Aalto, Finland ; Institute for Advanced Study and Department of Neurology, Klinikum Rechts der Isar, Technische Universit?t M?nchen M?nchen, Germany.},
      year = {2015},
      volume = {9},
      pages = {113},
      url = {http://dx.doi.org/10.3389/fnins.2015.00113},
      doi = {http://doi.org/10.3389/fnins.2015.00113}
    }
    
    Partridge, J.G. Utilizing GCaMP transgenic mice to monitor endogenous Gq/11-coupled receptors. 2015 Front Pharmacol
    Vol. 6, pp. 42School: Department of Pharmacology and Physiology, Georgetown University School of Medicine , Washington, DC, USA ; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine , Washington, DC, USA. 
    DOI URL 
    Abstract: The family of GCaMPs are engineered proteins that contain Ca(2+) binding
    motifs within a circularly permutated variant of the Aequorea Victoria
    green fluorescent protein (cp-GFP). The rapidly advancing field of
    utilizing GCaMP reporter constructs represents a major step forward
    in our ability to monitor intracellular Ca(2+) dynamics. With the
    use of these genetically encoded Ca(2+) sensors, investigators have
    studied activation of endogenous Gq types of G protein-coupled receptors
    (GPCRs) and subsequent rises in intracellular calcium. Escalations
    in intracellular Ca(2+) from GPCR activation can be faithfully monitored
    in space and time as an increase in fluorescent emission from these
    proteins. Further, transgenic mice are now commercially available
    that express GCaMPs in a Cre recombinase dependent fashion. These
    GCaMP reporter mice can be bred to distinct Cre recombinase driver
    mice to direct expression of this sensor in unique populations of
    cells. Concerning the central nervous system (CNS), sources of calcium
    influx, including those arising from Gq activation can be observed
    in targeted cell types like neurons or astrocytes. This powerful
    genetic method allows simultaneous monitoring of the activity of
    dozens of cells upon activation of endogenous Gq-coupled GPCRs. Therefore,
    in combination with pharmacological tools, this strategy of monitoring
    GPCR activation is amenable to analysis of orthosteric and allosteric
    ligands of Gq-coupled receptors in their endogenous environments.
    BibTeX:
    @article{Partridge2015,
      author = {Partridge, John G.},
      title = {Utilizing GCaMP transgenic mice to monitor endogenous Gq/11-coupled receptors.},
      journal = {Front Pharmacol},
      school = {Department of Pharmacology and Physiology, Georgetown University School of Medicine , Washington, DC, USA ; Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine , Washington, DC, USA.},
      year = {2015},
      volume = {6},
      pages = {42},
      url = {http://dx.doi.org/10.3389/fphar.2015.00042},
      doi = {http://doi.org/10.3389/fphar.2015.00042}
    }
    
    Petkov, C.I., Kikuchi, Y., Milne, A.E., Mishkin, M., Rauschecker, J.P. & Logothetis, N.K. Different forms of effective connectivity in primate frontotemporal pathways. 2015 Nat Commun
    Vol. 6, pp. 6000School: Division of Imaging Science and Biomedical Engineering, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. 
    DOI URL 
    Abstract: It is generally held that non-primary sensory regions of the brain
    have a strong impact on frontal cortex. However, the effective connectivity
    of pathways to frontal cortex is poorly understood. Here we microstimulate
    sites in the superior temporal and ventral frontal cortex of monkeys
    and use functional magnetic resonance imaging to evaluate the functional
    activity resulting from the stimulation of interconnected regions.
    Surprisingly, we find that, although certain earlier stages of auditory
    cortical processing can strongly activate frontal cortex, downstream
    auditory regions, such as voice-sensitive cortex, appear to functionally
    engage primarily an ipsilateral temporal lobe network. Stimulating
    other sites within this activated temporal lobe network shows strong
    activation of frontal cortex. The results indicate that the relative
    stage of sensory processing does not predict the level of functional
    access to the frontal lobes. Rather, certain brain regions engage
    local networks, only parts of which have a strong functional impact
    on frontal cortex.
    BibTeX:
    @article{Petkov2015,
      author = {Petkov, Christopher I. and Kikuchi, Yukiko and Milne, Alice E. and Mishkin, Mortimer and Rauschecker, Josef P. and Logothetis, Nikos K.},
      title = {Different forms of effective connectivity in primate frontotemporal pathways.},
      journal = {Nat Commun},
      school = { Division of Imaging Science and Biomedical Engineering, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK.},
      year = {2015},
      volume = {6},
      pages = {6000},
      url = {http://dx.doi.org/10.1038/ncomms7000},
      doi = {http://doi.org/10.1038/ncomms7000}
    }
    
    Rauschecker, J.P. Auditory and visual cortex of primates: a comparison of two sensory systems. 2015 Eur J Neurosci
    Vol. 41(5), pp. 579-585School: Department of Neuroscience, Georgetown University Medical Center, NRB WP19, 3970 Reservoir Rd NW, Washington, DC, 20057-1460, USA; Institute for Advanced Study, Technische Universit?t M?nchen, Garching, Germany. 
    DOI URL 
    Abstract: A comparative view of the brain, comparing related functions across
    species and sensory systems, offers a number of advantages. In particular,
    it allows separation of the formal purpose of a model structure from
    its implementation in specific brains. Models of auditory cortical
    processing can be conceived by analogy to the visual cortex, incorporating
    neural mechanisms that are found in both the visual and auditory
    systems. Examples of such canonical features at the columnar level
    are direction selectivity, size/bandwidth selectivity, and receptive
    fields with segregated vs. overlapping ON and OFF subregions. On
    a larger scale, parallel processing pathways have been envisioned
    that represent the two main facets of sensory perception: (i) identification
    of objects; and (ii) processing of space. Expanding this model in
    terms of sensorimotor integration and control offers an overarching
    view of cortical function independently of sensory modality.
    BibTeX:
    @article{Rauschecker2015,
      author = {Rauschecker, Josef P.},
      title = {Auditory and visual cortex of primates: a comparison of two sensory systems.},
      journal = {Eur J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, NRB WP19, 3970 Reservoir Rd NW, Washington, DC, 20057-1460, USA; Institute for Advanced Study, Technische Universit?t M?nchen, Garching, Germany.},
      year = {2015},
      volume = {41},
      number = {5},
      pages = {579--585},
      url = {http://dx.doi.org/10.1111/ejn.12844},
      doi = {http://doi.org/10.1111/ejn.12844}
    }
    
    Rozeboom, A.M., Queenan, B.N., Partridge, J.G., Farnham, C., Wu, J.-Y., Vicini, S. & Pak, D.T.S. Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity. 2015 Neurobiol Learn Mem
    Vol. 125, pp. 265-273School: Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA. Electronic address: Daniel.Pak@georgetown.edu. 
    DOI URL 
    Abstract: Hebbian, or associative, forms of synaptic plasticity are considered the molecular basis of learning and memory. However, associative synaptic modifications, including long-term potentiation (LTP) and depression (LTD), can form positive feedback loops which must be constrained for neural networks to remain stable. One proposed constraint mechanism is metaplasticity, a process whereby synaptic changes shift the threshold for subsequent plasticity. Metaplasticity has been functionally observed but the molecular basis is not well understood. Here, we report that stimulation which induces LTP recruits GluN2B-lacking GluN1/GluN3 NMDA receptors (NMDARs) to excitatory synapses of hippocampal pyramidal neurons. These unconventional receptors may compete against conventional GluN1/GluN2 NMDARs to favor synaptic depotentiation in response to subsequent "LTP-inducing" stimulation. These results implicate glycinergic GluN1/GluN3 NMDAR as molecular brakes on excessive synaptic strengthening, suggesting a role for these receptors in the brain that has previously been elusive.
    BibTeX:
    @article{RozeboomQueenanPartridgeEtAl2015,
      author = {Rozeboom, Aaron M. and Queenan, Bridget N. and Partridge, John G. and Farnham, Christina and Wu, Jian-Young and Vicini, Stefano and Pak, Daniel T S.},
      title = {Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity.},
      journal = {Neurobiol Learn Mem},
      school = { Physiology, Georgetown University Medical Center, Washington, DC 20057-1464, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA. Electronic address: Daniel.Pak@georgetown.edu.},
      year = {2015},
      volume = {125},
      pages = {265--273},
      url = {http://dx.doi.org/10.1016/j.nlm.2015.10.005},
      doi = {http://doi.org/10.1016/j.nlm.2015.10.005}
    }
    
    Ullman, M.T. & Pullman, M.Y. A compensatory role for declarative memory in neurodevelopmental disorders. 2015 Neurosci Biobehav Rev
    Vol. 51, pp. 205-222School: Brain and Language Laboratory, Department of Neuroscience, Georgetown University, Box 571464, Washington, DC 20057-1464, United States. 
    DOI URL 
    Abstract: Most research on neurodevelopmental disorders has focused on their
    abnormalities. However, what remains intact may also be important.
    Increasing evidence suggests that declarative memory, a critical
    learning and memory system in the brain, remains largely functional
    in a number of neurodevelopmental disorders. Because declarative
    memory remains functional in these disorders, and because it can
    learn and retain numerous types of information, functions, and tasks,
    this system should be able to play compensatory roles for multiple
    types of impairments across the disorders. Here, we examine this
    hypothesis for specific language impairment, dyslexia, autism spectrum
    disorder, Tourette syndrome, and obsessive-compulsive disorder. We
    lay out specific predictions for the hypothesis and review existing
    behavioral, electrophysiological, and neuroimaging evidence. Overall,
    the evidence suggests that declarative memory indeed plays compensatory
    roles for a range of impairments across all five disorders. Finally,
    we discuss diagnostic, therapeutic and other implications.
    BibTeX:
    @article{Ullman2015,
      author = {Ullman, Michael T. and Pullman, Mariel Y.},
      title = {A compensatory role for declarative memory in neurodevelopmental disorders.},
      journal = {Neurosci Biobehav Rev},
      school = {Brain and Language Laboratory, Department of Neuroscience, Georgetown University, Box 571464, Washington, DC 20057-1464, United States.},
      year = {2015},
      volume = {51},
      pages = {205--222},
      url = {http://dx.doi.org/10.1016/j.neubiorev.2015.01.008},
      doi = {http://doi.org/10.1016/j.neubiorev.2015.01.008}
    }
    
    Valente, M.M., Allen, M., Bortolotto, V., Lim, S.T., Conant, K. & Grilli, M. The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells. 2015 Neural Plast
    Vol. 2015, pp. 646595School: , 28100 Novara, Italy. 
    DOI URL 
    Abstract: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a role in varied forms of developmental and postnatal neuroplasticity. MMP substrates include protease-activated receptor-1 (PAR-1), a G-protein coupled receptor expressed in hippocampus. We examined proliferation and differentiation of adult neural progenitor cells (aNPCs) from hippocampi of mice that overexpress the potent PAR-1 agonist MMP-1. We found that, as compared to aNPCs from littermate controls, MMP-1 tg aNPCs display enhanced proliferation. Under differentiating conditions, these cells give rise to a higher percentage of MAP-2(+) neurons and a reduced number of oligodendrocyte precursors, and no change in the number of astrocytes. The fact that these results are MMP and PAR-1 dependent is supported by studies with distinct antagonists. Moreover, JSH-23, an inhibitor of NF-?B p65 nuclear translocation, counteracted both the proliferation and differentiation changes seen in MMP-1 tg-derived NPCs. In complementary studies, we found that the percentage of Sox2(+) undifferentiated progenitor cells is increased in hippocampi of MMP-1 tg animals, compared to wt mice. Together, these results add to a growing body of data suggesting that MMPs are effectors of hippocampal neuroplasticity in the adult CNS and that the MMP-1/PAR-1 axis may play a role in neurogenesis following physiological and/or pathological stimuli.
    BibTeX:
    @article{ValenteAllenBortolottoEtAl2015,
      author = {Valente, Maria Maddalena and Allen, Megan and Bortolotto, Valeria and Lim, Seung T. and Conant, Katherine and Grilli, Mariagrazia},
      title = {The MMP-1/PAR-1 Axis Enhances Proliferation and Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells.},
      journal = {Neural Plast},
      school = {, 28100 Novara, Italy.},
      year = {2015},
      volume = {2015},
      pages = {646595},
      url = {http://dx.doi.org/10.1155/2015/646595},
      doi = {http://doi.org/10.1155/2015/646595}
    }
    
    Washington, S.D. & Tillinghast, J.S. Conjugating time and frequency: hemispheric specialization, acoustic uncertainty, and the mustached bat. 2015 Front Neurosci
    Vol. 9, pp. 143School: Department of Mathematics and Statistics, American University Washington, DC, USA ; Department of Statistics, The George Washington University Washington, DC, USA. 
    DOI URL 
    Abstract: A prominent hypothesis of hemispheric specialization for human speech
    and music states that the left and right auditory cortices (ACs)
    are respectively specialized for precise calculation of two canonically-conjugate
    variables: time and frequency. This spectral-temporal asymmetry does
    not account for sex, brain-volume, or handedness, and is in opposition
    to closed-system hypotheses that restrict this asymmetry to humans.
    Mustached bats have smaller brains, but greater ethological pressures
    to develop such a spectral-temporal asymmetry, than humans. Using
    the Heisenberg-Gabor Limit (i.e., the mathematical basis of the spectral-temporal
    asymmetry) to frame mustached bat literature, we show that recent
    findings in bat AC (1) support the notion that hemispheric specialization
    for speech and music is based on hemispheric differences in temporal
    and spectral resolution, (2) discredit closed-system, handedness,
    and brain-volume theories, (3) underscore the importance of sex differences,
    and (4) provide new avenues for phonological research.
    BibTeX:
    @article{Washington2015,
      author = {Washington, Stuart D. and Tillinghast, John S.},
      title = {Conjugating time and frequency: hemispheric specialization, acoustic uncertainty, and the mustached bat.},
      journal = {Front Neurosci},
      school = {Department of Mathematics and Statistics, American University Washington, DC, USA ; Department of Statistics, The George Washington University Washington, DC, USA.},
      year = {2015},
      volume = {9},
      pages = {143},
      url = {http://dx.doi.org/10.3389/fnins.2015.00143},
      doi = {http://doi.org/10.3389/fnins.2015.00143}
    }
    
    Wurzman, R., Forcelli, P.A., Griffey, C.J. & Kromer, L.F. Repetitive grooming and sensorimotor abnormalities in an ephrin-A knockout model for Autism Spectrum Disorders. 2015 Behav Brain Res
    Vol. 278, pp. 115-128School: Georgetown University, Department of Neuroscience, Washington, DC 20057, United States of America; Georgetown University, Interdisciplinary Program in Neuroscience, Washington, DC 20057, United States of America. 
    DOI URL 
    Abstract: EphA receptors and ephrin-A ligands play important roles in neural
    development and synaptic plasticity in brain regions where expression
    persists into adulthood. Recently, EPHA3 and EPHA7 gene mutations
    were linked with Autism Spectrum Disorders (ASDs) and developmental
    neurological delays, respectively. Furthermore, deletions of ephrin-A2
    or ephrin-A3, which exhibit high binding affinity for EphA3 and EphA7
    receptors, are associated with subtle deficits in learning and memory
    behavior and abnormalities in dendritic spine morphology in the cortex
    and hippocampus in mice. To better characterize a potential role
    for these ligands in ASDs, we performed a comprehensive behavioral
    characterization of anxiety-like, sensorimotor, learning, and social
    behaviors in ephrin-A2/-A3 double knockout (DKO) mice. The predominant
    phenotype in DKO mice was repetitive and self-injurious grooming
    behaviors such as have been associated with corticostriatal circuit
    abnormalities in other rodent models of neuropsychiatric disorders.
    Consistent with ASDs specifically, DKO mice exhibited decreased preference
    for social interaction in the social approach assay, decreased locomotor
    activity in the open field, increased prepulse inhibition of acoustic
    startle, and a shift towards self-directed activity (e.g., grooming)
    in novel environments, such as marble burying. Although there were
    no gross deficits in cognitive assays, subtle differences in performance
    on fear conditioning and in the Morris water maze resembled traits
    observed in other rodent models of ASD. We therefore conclude that
    ephrin-A2/-A3 DKO mice have utility as a novel ASD model with an
    emphasis on sensory abnormalities and restricted, repetitive behavioral
    symptoms.
    BibTeX:
    @article{Wurzman2015,
      author = {Wurzman, Rachel and Forcelli, Patrick A. and Griffey, Christopher J. and Kromer, Lawrence F.},
      title = {Repetitive grooming and sensorimotor abnormalities in an ephrin-A knockout model for Autism Spectrum Disorders.},
      journal = {Behav Brain Res},
      school = {Georgetown University, Department of Neuroscience, Washington, DC 20057, United States of America; Georgetown University, Interdisciplinary Program in Neuroscience, Washington, DC 20057, United States of America.},
      year = {2015},
      volume = {278},
      pages = {115--128},
      url = {http://dx.doi.org/10.1016/j.bbr.2014.09.012},
      doi = {http://doi.org/10.1016/j.bbr.2014.09.012}
    }
    
    Zhou, Y., Zhao, W., Al-Muhtasib, N. & Rebeck, G.W. APOE Genotype Alters Immunoglobulin Subtypes in Knock-In Mice. 2015 J Alzheimers DisSchool: Department of Neuroscience, Georgetown University, Washington, DC, USA.  DOI URL 
    Abstract: Apolipoprotein E (APOE) alleles are strongly related to the risk of
    Alzheimer's disease (AD). APOE genotype also affects inflammatory
    processes in response to damage. We tested whether APOE genotype
    affected the levels of specific immunoglobulins in healthy, uninfected
    APOE knock-in mice. We measured specific immunoglobulins in brain,
    spleen, and plasma. Levels of total IgG in brain and spleen were
    highest in APOE-?3 mice, significantly higher than in APOE-?2 and
    APOE-?4 mice; no differences were observed for levels of total IgG
    plasma. We also measured specific subtypes of IgG. IgG1 was only
    detectable in plasma and did not differ by APOE genotype. IgG3 was
    detectable in plasma and spleen, and also did not differ by APOE
    genotype. IgG2b showed the same pattern as levels of total IgG by
    APOE genotype, with the highest levels of IgG2b in brain, spleen,
    and plasma of APOE-?3 mice. IgG2a showed an entirely different pattern,
    with significantly higher levels in spleen and plasma of APOE-?4
    mice compared to APOE-?2 and APOE-?3 mice. We also measured IgM and
    IgA in spleens and plasma of these mice. In spleen, APOE-?4 mice
    had the lowest IgA levels and the highest levels of IgM; both being
    significantly different from APOE-?2 mice. In total, murine IgG2a
    and IgM were highest in APOE-?4 mice, while total IgG and Ig2b were
    highest in APOE-?3 mice. These dramatically different distributions
    of immunoglobulins could allow for human AD risk biomarkers based
    on specific immunoglobulin subtypes.
    BibTeX:
    @article{Zhou2015,
      author = {Zhou, Ye and Zhao, Wenjuan and Al-Muhtasib, Nour and Rebeck, G William},
      title = {APOE Genotype Alters Immunoglobulin Subtypes in Knock-In Mice.},
      journal = {J Alzheimers Dis},
      school = {Department of Neuroscience, Georgetown University, Washington, DC, USA.},
      year = {2015},
      url = {http://dx.doi.org/10.3233/JAD-142184},
      doi = {http://doi.org/10.3233/JAD-142184}
    }
    
    Anurova, I., Renier, L.A., De Volder, A.G., Carlson, S. & Rauschecker, J.P. Relationship Between Cortical Thickness and Functional Activation in the Early Blind. 2014 Cereb CortexSchool: y Medical Center, Washington, DC 20057, USA.  DOI URL 
    Abstract: Early blindness results in both structural and functional changes
    of the brain. However, these changes have rarely been studied in
    relation to each other. We measured alterations in cortical thickness
    (CT) caused by early visual deprivation and their relationship with
    cortical activity. Structural and functional magnetic resonance imaging
    was performed in 12 early blind (EB) humans and 12 sighted controls
    (SC). Experimental conditions included one-back tasks for auditory
    localization and pitch identification, and a simple sound-detection
    task. Structural and functional data were analyzed in a whole-brain
    approach and within anatomically defined regions of interest in sensory
    areas of the spared (auditory) and deprived (visual) modalities.
    Functional activation during sound-localization or pitch-identification
    tasks correlated negatively with CT in occipital areas of EB (calcarine
    sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus)
    and in nonprimary auditory areas of SC. These results suggest a link
    between CT and activation and demonstrate that the relationship between
    cortical structure and function may depend on early sensory experience,
    probably via selective pruning of exuberant connections. Activity-dependent
    effects of early sensory deprivation and long-term practice are superimposed
    on normal maturation and aging. Together these processes shape the
    relationship between brain structure and function over the lifespan.
    BibTeX:
    @article{Anurova2014,
      author = {Anurova, Irina and Renier, Laurent A. and De Volder, Anne G. and Carlson, Synn?ve and Rauschecker, Josef P.},
      title = {Relationship Between Cortical Thickness and Functional Activation in the Early Blind.},
      journal = {Cereb Cortex},
      school = {y Medical Center, Washington, DC 20057, USA.},
      year = {2014},
      url = {http://dx.doi.org/10.1093/cercor/bhu009},
      doi = {http://doi.org/10.1093/cercor/bhu009}
    }
    
    Buniak, L., Darragh, M. & Giordano, J. A four-part working bibliography of neuroethics: part 1: overview and reviews--defining and describing the field and its practices. 2014 Philos Ethics Humanit Med
    Vol. 9, pp. 9School: Neuroethics Studies Program, Edmund D, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, Washington, DC 20057, USA. jg353@georgetown.edu. 
    DOI URL 
    Abstract: Neuroethics entails investigations of neurocognitive mechanisms of
    morality and ethics; and studies and address of the ethical issues
    spawned by the use of neuroscience and its technologies to investigate
    cognition, emotion and actions. These two principal emphases, or
    what have been called "traditions" of neuroethics both mirror traditional
    bioethical discussions (such as debates about the safety of technological
    and pharmaceutical advances and ethical implications of new scientific
    and technological discoveries), and engage discourse about neuroscientific
    investigations of (proto-moral and moral) cognition, emotions and
    behaviors, and what such findings may mean for human beliefs and
    conduct - from the individual to the political levels.Given the growth,
    range, and rapid maturation of the field of neuroethics we provide
    an iterative, four-part document that affords a repository of international
    papers, books, and chapters that address the field in overview, and
    present discussion(s) of more particular aspects and topics of neuroethics.
    This first installment lists reviews and overviews of the discipline,
    and broad summaries of basic developments and issues of the field.To
    systematically survey the neuroethics literature, searches were performed
    by accessing 11 databases, 8 additional literature depositories,
    and 4 individual journal searches using indexing language for National
    Library of Medicine (NLM) Medical Subject Heading databases. Searches
    and assurance against overlapping coverage were conducted using the
    RefWorks citation management program.Overview, review and reflections
    upon the history and multicultural perspectives of neuroethics were
    obtained and relevant listings from international journals, books,
    and book chapters are provided. Part I will be followed by three
    installments that will address a): the neuroscience of morality and
    ethics, including discussions of free will, and personal autonomy;
    b) "second tradition neuroethics", to include specific ethical issues
    in neuroscience; clinical neuroethics; and c) neuroethics education/training;
    neuroethics and society; neuroethics and law; neuroethics and policy;
    and international neuroethics.
    BibTeX:
    @article{Buniak2014,
      author = {Buniak, Liana and Darragh, Martina and Giordano, James},
      title = {A four-part working bibliography of neuroethics: part 1: overview and reviews--defining and describing the field and its practices.},
      journal = {Philos Ethics Humanit Med},
      school = {Neuroethics Studies Program, Edmund D, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, Washington, DC 20057, USA. jg353@georgetown.edu.},
      year = {2014},
      volume = {9},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1747-5341-9-9},
      doi = {http://doi.org/10.1186/1747-5341-9-9}
    }
    
    Burrell, T.C., Divekar, S.D., Weeber, E.J. & Rebeck, G.W. Fyn tyrosine kinase increases Apolipoprotein E Receptor 2 levels and phosphorylation. 2014 PLoS One
    Vol. 9(10), pp. e110845School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America. 
    DOI URL 
    Abstract: Apolipoprotein E Receptor 2 (ApoER2) and the tyrosine kinase Fyn are
    both members of the Reelin pathway, a signaling pathway essential
    for the laminar formation of the cortex during development and proper
    dendritic spine density and long-term potential (LTP) in the adult
    brain. In the presence of extracellular Reelin, ApoER2 binds the
    intracellular protein Dab1, an adaptor protein that is phosphorylated
    by Fyn. However, direct interactions between ApoER2 and Fyn are not
    well defined. Here, we show that total levels of ApoER2 and surface
    levels of ApoER2 are increased by active Fyn. Via a separate mechanism,
    ApoER2 is also phosphorylated by Fyn, an event that peaks in the
    postnatal cortex at day 5 and can occur at multiple ApoER2 tyrosine
    residues. Dab1 is also involved in this phosphorylation, promoting
    the phosphorylation of ApoER2 by Fyn when it is itself phosphorylated.
    These results elucidate some of the intracellular mechanisms that
    give rise to a functional Reelin pathway.
    BibTeX:
    @article{Burrell2014,
      author = {Burrell, Teal C. and Divekar, Shailaja D. and Weeber, Edwin J. and Rebeck, G William},
      title = {Fyn tyrosine kinase increases Apolipoprotein E Receptor 2 levels and phosphorylation.},
      journal = {PLoS One},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America.},
      year = {2014},
      volume = {9},
      number = {10},
      pages = {e110845},
      url = {http://dx.doi.org/10.1371/journal.pone.0110845},
      doi = {http://doi.org/10.1371/journal.pone.0110845}
    }
    
    Chu, C.C.J., Chien, P.F. & Hung, C.P. Tuning dissimilarity explains short distance decline of spontaneous spike correlation in macaque V1. 2014 Vision Res
    Vol. 96, pp. 113-132School: Institute of Neuroscience and Brain Research Center, National Yang-Ming Univ., Taipei 112, Taiwan; Dept. of Neuroscience, Georgetown University, 3970 Reservoir Rd. NW, NRB EP-04, Washington, DC 20007, United States. Electronic address: ch486@georgetown.edu. 
    DOI URL 
    Abstract: Fast spike correlation is a signature of neural ensemble activity
    thought to underlie perception, cognition, and action. To relate
    spike correlation to tuning and other factors, we focused on spontaneous
    activity because it is the common 'baseline' across studies that
    test different stimuli, and because variations in correlation strength
    are much larger across cell pairs than across stimuli. Is the probability
    of spike correlation between two neurons a graded function of lateral
    cortical separation, independent of functional tuning (e.g. orientation
    preferences)? Although previous studies found a steep decline in
    fast spike correlation with horizontal cortical distance, we hypothesized
    that, at short distances, this decline is better explained by a decline
    in receptive field tuning similarity. Here we measured macaque V1
    tuning via parametric stimuli and spike-triggered analysis, and we
    developed a generalized linear model (GLM) to examine how different
    combinations of factors predict spontaneous spike correlation. Spike
    correlation was predicted by multiple factors including color, spatiotemporal
    receptive field, spatial frequency, phase and orientation but not
    ocular dominance beyond layer 4. Including these factors in the model
    mostly eliminated the contribution of cortical distance to fast spike
    correlation (up to our recording limit of 1.4mm), in terms of both
    'correlation probability' (the incidence of pairs that have significant
    fast spike correlation) and 'correlation strength' (each pair's likelihood
    of fast spike correlation). We suggest that, at short distances and
    non-input layers, V1 fast spike correlation is determined more by
    tuning similarity than by cortical distance or ocular dominance.
    BibTeX:
    @article{Chu2014,
      author = {Chu, Cheng C J. and Chien, Ping F. and Hung, Chou P.},
      title = {Tuning dissimilarity explains short distance decline of spontaneous spike correlation in macaque V1.},
      journal = {Vision Res},
      school = {Institute of Neuroscience and Brain Research Center, National Yang-Ming Univ., Taipei 112, Taiwan; Dept. of Neuroscience, Georgetown University, 3970 Reservoir Rd. NW, NRB EP-04, Washington, DC 20007, United States. Electronic address: ch486@georgetown.edu.},
      year = {2014},
      volume = {96},
      pages = {113--132},
      url = {http://dx.doi.org/10.1016/j.visres.2014.01.008},
      doi = {http://doi.org/10.1016/j.visres.2014.01.008}
    }
    
    Clark, G.M., Lum, J.A.G. & Ullman, M.T. A meta-analysis and meta-regression of serial reaction time task performance in Parkinson's disease. 2014 Neuropsychology
    Vol. 28(6), pp. 945-958School: Department of Neuroscience, Georgetown University. 
    DOI URL 
    Abstract: This article reports findings of a meta-analysis and meta-regression
    summarizing research on implicit sequence learning in individuals
    with Parkinson's disease (PD), as measured by the Serial Reaction
    Time (SRT) task.Following a systematic search of the literature,
    we analyzed a total of 27 studies, representing data from 505 participants
    with PD and 460 neurologically intact control participants.Overall,
    the meta-analysis indicated significantly (p < .001) worse sequence
    learning by the PD group than the control group. The average weighted
    effect size was found to be .531 (95% CI [.332, .470]), which is
    a medium effect size. However, moderate to high levels of heterogeneity
    (differences) were found between study effect sizes (I(2) = 58.
    Meta-regression analysis suggested that presentation of the SRT task
    under dual task conditions coupled with PD severity or characteristics
    of the sequence might affect study effect sizes.The meta-analysis
    provides clear support that learning in procedural memory (procedural
    learning), which underlies implicit sequence learning in the SRT
    task, is impaired in PD.
    BibTeX:
    @article{Clark2014,
      author = {Clark, Gillian M. and Lum, Jarrad A G. and Ullman, Michael T.},
      title = {A meta-analysis and meta-regression of serial reaction time task performance in Parkinson's disease.},
      journal = {Neuropsychology},
      school = {Department of Neuroscience, Georgetown University.},
      year = {2014},
      volume = {28},
      number = {6},
      pages = {945--958},
      url = {http://dx.doi.org/10.1037/neu0000121},
      doi = {http://doi.org/10.1037/neu0000121}
    }
    
    Clifford, M.A., Athar, W., Leonard, C.E., Russo, A., Sampognaro, P.J., Van der Goes, M.-S., Burton, D.A., Zhao, X., Lalchandani, R.R., Sahin, M., Vicini, S. & Donoghue, M.J. EphA7 signaling guides cortical dendritic development and spine maturation. 2014 Proc Natl Acad Sci U S A
    Vol. 111(13), pp. 4994-4999School: Departments of Biology and Pharmacology and Physiology, Interdisciplinary Program in Neuroscience, and Graduate Program in Physiology and Biophysics, Georgetown University, Washington, DC 20057. 
    DOI URL 
    Abstract: The process by which excitatory neurons are generated and mature during
    the development of the cerebral cortex occurs in a stereotyped manner;
    coordinated neuronal birth, migration, and differentiation during
    embryonic and early postnatal life are prerequisites for selective
    synaptic connections that mediate meaningful neurotransmission in
    maturity. Normal cortical function depends upon the proper elaboration
    of neurons, including the initial extension of cellular processes
    that lead to the formation of axons and dendrites and the subsequent
    maturation of synapses. Here, we examine the role of cell-based signaling
    via the receptor tyrosine kinase EphA7 in guiding the extension and
    maturation of cortical dendrites. EphA7, localized to dendritic shafts
    and spines of pyramidal cells, is uniquely expressed during cortical
    neuronal development. On patterned substrates, EphA7 signaling restricts
    dendritic extent, with Src and Tsc1 serving as downstream mediators.
    Perturbation of EphA7 signaling in vitro and in vivo alters dendritic
    elaboration: Dendrites are longer and more complex when EphA7 is
    absent and are shorter and simpler when EphA7 is ectopically expressed.
    Later in neuronal maturation, EphA7 influences protrusions from dendritic
    shafts and the assembling of synaptic components. Indeed, synaptic
    function relies on EphA7; the electrophysiological maturation of
    pyramidal neurons is delayed in cultures lacking EphA7, indicating
    that EphA7 enhances synaptic function. These results provide evidence
    of roles for Eph signaling, first in limiting the elaboration of
    cortical neuronal dendrites and then in coordinating the maturation
    and function of synapses.
    BibTeX:
    @article{Clifford2014,
      author = {Clifford, Meredith A. and Athar, Wardah and Leonard, Carrie E. and Russo, Alexandra and Sampognaro, Paul J. and Van der Goes, Marie-Sophie and Burton, Denver A. and Zhao, Xiumei and Lalchandani, Rupa R. and Sahin, Mustafa and Vicini, Stefano and Donoghue, Maria J.},
      title = {EphA7 signaling guides cortical dendritic development and spine maturation.},
      journal = {Proc Natl Acad Sci U S A},
      school = {Departments of Biology and Pharmacology and Physiology, Interdisciplinary Program in Neuroscience, and Graduate Program in Physiology and Biophysics, Georgetown University, Washington, DC 20057.},
      year = {2014},
      volume = {111},
      number = {13},
      pages = {4994--4999},
      url = {http://dx.doi.org/10.1073/pnas.1323793111},
      doi = {http://doi.org/10.1073/pnas.1323793111}
    }
    
    Cowdin, N., Kobayashi, I. & Mellman, T.A. Theta frequency activity during rapid eye movement (REM) sleep is greater in people with resilience versus PTSD. 2014 Exp Brain Res
    Vol. 232(5), pp. 1479-1485School: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA. 
    DOI URL 
    Abstract: Emotional memory consolidation has been associated with rapid eye
    movement (REM) sleep, and recent evidence suggests that increased
    electroencephalogram spectral power in the theta (4-8 Hz) frequency
    range indexes this activity. REM sleep has been implicated in posttraumatic
    stress disorder (PTSD) as well as in emotional adaption. In this
    cross-sectional study, thirty young healthy African American adults
    with trauma exposure were assessed for PTSD status using the Clinician
    Administered PTSD Scale. Two consecutive night polysomnographic (PSG)
    recordings were performed and data scored for sleep stages. Quantitative
    electroencephalographic spectral analysis was used to measure theta
    frequency components sampled from REM sleep periods of the second-night
    PSG recordings. Our objective was to compare relative theta power
    between trauma-exposed participants who were either resilient or
    had developed PTSD. Results indicated higher right prefrontal theta
    power during the first and last REM periods in resilient participants
    compared with participants with PTSD. Right hemisphere prefrontal
    theta power during REM sleep may serve as a biomarker of the capacity
    for adaptive emotional memory processing among trauma-exposed individuals.
    BibTeX:
    @article{Cowdin2014,
      author = {Cowdin, Nancy and Kobayashi, Ihori and Mellman, Thomas A.},
      title = {Theta frequency activity during rapid eye movement (REM) sleep is greater in people with resilience versus PTSD.},
      journal = {Exp Brain Res},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.},
      year = {2014},
      volume = {232},
      number = {5},
      pages = {1479--1485},
      url = {http://dx.doi.org/10.1007/s00221-014-3857-5},
      doi = {http://doi.org/10.1007/s00221-014-3857-5}
    }
    
    Daniele, S.G., Edwards, A.A. & Maguire-Zeiss, K.A. Isolation of cortical microglia with preserved immunophenotype and functionality from murine neonates. 2014 J Vis Exp(83), pp. e51005School: Department of Neuroscience, Georgetown University Medical Center.  DOI URL 
    Abstract: Isolation of microglia from CNS tissue is a powerful investigative
    tool used to study microglial biology ex vivo. The present method
    details a procedure for isolation of microglia from neonatal murine
    cortices by mechanical agitation with a rotary shaker. This microglia
    isolation method yields highly pure cortical microglia that exhibit
    morphological and functional characteristics indicative of quiescent
    microglia in normal, nonpathological conditions in vivo. This procedure
    also preserves the microglial immunophenotype and biochemical functionality
    as demonstrated by the induction of morphological changes, nuclear
    translocation of the p65 subunit of NF-?B (p65), and secretion of
    the hallmark proinflammatory cytokine, tumor necrosis factor-? (TNF-?),
    upon lipopolysaccharide (LPS) and Pam3CSK4 (Pam) challenges. Therefore,
    the present isolation procedure preserves the immunophenotype of
    both quiescent and activated microglia, providing an experimental
    method of investigating microglia biology in ex vivo conditions.
    BibTeX:
    @article{Daniele2014,
      author = {Daniele, Stefano G. and Edwards, Amanda A. and Maguire-Zeiss, Kathleen A.},
      title = {Isolation of cortical microglia with preserved immunophenotype and functionality from murine neonates.},
      journal = {J Vis Exp},
      school = {Department of Neuroscience, Georgetown University Medical Center.},
      year = {2014},
      number = {83},
      pages = {e51005},
      url = {http://dx.doi.org/10.3791/51005},
      doi = {http://doi.org/10.3791/51005}
    }
    
    DiBattista, A.M., Stevens, B.W., Rebeck, G.W. & Green, A.E. Two Alzheimer's disease risk genes increase entorhinal cortex volume in young adults. 2014 Front Hum Neurosci
    Vol. 8, pp. 779School: Department of Psychology, Georgetown University Washington, DC, USA. 
    DOI URL 
    Abstract: Alzheimer's disease (AD) risk genes alter brain structure and function
    decades before disease onset. Apolipoprotein E (APOE) is the strongest
    known genetic risk factor for AD, and a related gene, apolipoprotein
    J (APOJ), also affects disease risk. However, the extent to which
    these genes affect brain structure in young adults remains unclear.
    Here, we report that AD risk alleles of these two genes, APOE-?4
    and APOJ-C, cumulatively alter brain volume in young adults. Using
    voxel-based morphometry (VBM) in 57 individuals, we examined the
    entorhinal cortex, one of the earliest brain regions affected in
    AD pathogenesis. Apolipoprotein E-?4 carriers exhibited higher right
    entorhinal cortex volume compared to non-carriers. Interestingly,
    APOJ-C risk genotype was associated with higher bilateral entorhinal
    cortex volume in non-APOE-?4 carriers. To determine the combined
    disease risk of APOE and APOJ status per subject, we used cumulative
    odds ratios as regressors for volumetric measurements. Higher disease
    risk corresponded to greater right entorhinal cortex volume. These
    results suggest that, years before disease onset, two key AD genetic
    risk factors may exert influence on the structure of a brain region
    where AD pathogenesis takes root.
    BibTeX:
    @article{DiBattista2014,
      author = {DiBattista, Amanda Marie and Stevens, Benson W. and Rebeck, G William and Green, Adam E.},
      title = {Two Alzheimer's disease risk genes increase entorhinal cortex volume in young adults.},
      journal = {Front Hum Neurosci},
      school = {Department of Psychology, Georgetown University Washington, DC, USA.},
      year = {2014},
      volume = {8},
      pages = {779},
      url = {http://dx.doi.org/10.3389/fnhum.2014.00779},
      doi = {http://doi.org/10.3389/fnhum.2014.00779}
    }
    
    Divekar, S.D., Burrell, T.C., Lee, J.E., Weeber, E.J. & Rebeck, G.W. Ligand-induced homotypic and heterotypic clustering of apolipoprotein E receptor 2. 2014 J Biol Chem
    Vol. 289(23), pp. 15894-15903School: From the Department of Neuroscience, Georgetown University Medical Center, Washington, D. C. 20007 and gwr2@georgetown.edu. 
    DOI URL 
    Abstract: ApoE Receptor 2 (ApoER2) and the very low density lipoprotein receptor
    (VLDLR) are type I transmembrane proteins belonging to the LDLR family
    of receptors. They are neuronal proteins found in synaptic compartments
    that play an important role in neuronal migration during development.
    ApoER2 and VLDLR bind to extracellular glycoproteins, such as Reelin
    and F-spondin, which leads to phosphorylation of adaptor proteins
    and subsequent activation of downstream signaling pathways. It is
    thought that ApoER2 and VLDLR undergo clustering upon binding to
    their ligands, but no direct evidence of clustering has been shown.
    Here we show strong clustering of ApoER2 induced by the dimeric ligands
    Fc-RAP, F-spondin, and Reelin but relatively weak clustering with
    the ligand apoE in the absence of lipoproteins. This clustering involves
    numerous proteins besides ApoER2, including amyloid precursor protein
    and the synaptic adaptor protein PSD-95. Interestingly, we did not
    observe strong clustering of ApoER2 with VLDLR. Clustering was modulated
    by both extracellular and intracellular domains of ApoER2. Together,
    our data demonstrate that several multivalent ligands for ApoER2
    induce clustering in transfected cells and primary neurons and that
    these complexes included other synaptic molecules, such as APP and
    PSD-95.
    BibTeX:
    @article{Divekar2014,
      author = {Divekar, Shailaja D. and Burrell, Teal C. and Lee, Jennifer E. and Weeber, Edwin J. and Rebeck, G William},
      title = {Ligand-induced homotypic and heterotypic clustering of apolipoprotein E receptor 2.},
      journal = {J Biol Chem},
      school = {From the Department of Neuroscience, Georgetown University Medical Center, Washington, D. C. 20007 and gwr2@georgetown.edu.},
      year = {2014},
      volume = {289},
      number = {23},
      pages = {15894--15903},
      url = {http://dx.doi.org/10.1074/jbc.M113.537548},
      doi = {http://doi.org/10.1074/jbc.M113.537548}
    }
    
    Erickson, L.C., Heeg, E., Rauschecker, J.P. & Turkeltaub, P.E. An ALE meta-analysis on the audiovisual integration of speech signals. 2014 Hum Brain MappSchool: Department of Neurology, Georgetown University Medical Center, Washington, District of Columbia; Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia.  DOI URL 
    Abstract: The brain improves speech processing through the integration of audiovisual
    (AV) signals. Situations involving AV speech integration may be crudely
    dichotomized into those where auditory and visual inputs contain
    (1) equivalent, complementary signals (validating AV speech) or (2)
    inconsistent, different signals (conflicting AV speech). This simple
    framework may allow the systematic examination of broad commonalities
    and differences between AV neural processes engaged by various experimental
    paradigms frequently used to study AV speech integration. We conducted
    an activation likelihood estimation metaanalysis of 22 functional
    imaging studies comprising 33 experiments, 311 subjects, and 347
    foci examining "conflicting" versus "validating" AV speech. Experimental
    paradigms included content congruency, timing synchrony, and perceptual
    measures, such as the McGurk effect or synchrony judgments, across
    AV speech stimulus types (sublexical to sentence). Colocalization
    of conflicting AV speech experiments revealed consistency across
    at least two contrast types (e.g., synchrony and congruency) in a
    network of dorsal stream regions in the frontal, parietal, and temporal
    lobes. There was consistency across all contrast types (synchrony,
    congruency, and percept) in the bilateral posterior superior/middle
    temporal cortex. Although fewer studies were available, validating
    AV speech experiments were localized to other regions, such as ventral
    stream visual areas in the occipital and inferior temporal cortex.
    These results suggest that while equivalent, complementary AV speech
    signals may evoke activity in regions related to the corroboration
    of sensory input, conflicting AV speech signals recruit widespread
    dorsal stream areas likely involved in the resolution of conflicting
    sensory signals. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals,
    Inc.
    BibTeX:
    @article{Erickson2014,
      author = {Erickson, Laura C. and Heeg, Elizabeth and Rauschecker, Josef P. and Turkeltaub, Peter E.},
      title = {An ALE meta-analysis on the audiovisual integration of speech signals.},
      journal = {Hum Brain Mapp},
      school = {Department of Neurology, Georgetown University Medical Center, Washington, District of Columbia; Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia.},
      year = {2014},
      url = {http://dx.doi.org/10.1002/hbm.22572},
      doi = {http://doi.org/10.1002/hbm.22572}
    }
    
    Erickson, L.C., Zielinski, B.A., Zielinski, J.E.V., Liu, G., Turkeltaub, P.E., Leaver, A.M. & Rauschecker, J.P. Distinct cortical locations for integration of audiovisual speech and the McGurk effect. 2014 Front Psychol
    Vol. 5, pp. 534School: Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA ; Department of Physiology and Biophysics, Georgetown University Medical Center, Washington DC, USA. 
    DOI URL 
    Abstract: Audiovisual (AV) speech integration is often studied using the McGurk
    effect, where the combination of specific incongruent auditory and
    visual speech cues produces the perception of a third illusory speech
    percept. Recently, several studies have implicated the posterior
    superior temporal sulcus (pSTS) in the McGurk effect; however, the
    exact roles of the pSTS and other brain areas in "correcting" differing
    AV sensory inputs remain unclear. Using functional magnetic resonance
    imaging (fMRI) in ten participants, we aimed to isolate brain areas
    specifically involved in processing congruent AV speech and the McGurk
    effect. Speech stimuli were composed of sounds and/or videos of consonant-vowel
    tokens resulting in four stimulus classes: congruent AV speech (AVCong),
    incongruent AV speech resulting in the McGurk effect (AVMcGurk),
    acoustic-only speech (AO), and visual-only speech (VO). In group-
    and single-subject analyses, left pSTS exhibited significantly greater
    fMRI signal for congruent AV speech (i.e., AVCong trials) than for
    both AO and VO trials. Right superior temporal gyrus, medial prefrontal
    cortex, and cerebellum were also identified. For McGurk speech (i.e.,
    AVMcGurk trials), two clusters in the left posterior superior temporal
    gyrus (pSTG), just posterior to Heschl's gyrus or on its border,
    exhibited greater fMRI signal than both AO and VO trials. We propose
    that while some brain areas, such as left pSTS, may be more critical
    for the integration of AV speech, other areas, such as left pSTG,
    may generate the "corrected" or merged percept arising from conflicting
    auditory and visual cues (i.e., as in the McGurk effect). These findings
    are consistent with the concept that posterior superior temporal
    areas represent part of a "dorsal auditory stream," which is involved
    in multisensory integration, sensorimotor control, and optimal state
    estimation (Rauschecker and Scott, 2009).
    BibTeX:
    @article{Erickson2014a,
      author = {Erickson, Laura C. and Zielinski, Brandon A. and Zielinski, Jennifer E V. and Liu, Guoying and Turkeltaub, Peter E. and Leaver, Amber M. and Rauschecker, Josef P.},
      title = {Distinct cortical locations for integration of audiovisual speech and the McGurk effect.},
      journal = {Front Psychol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA ; Department of Physiology and Biophysics, Georgetown University Medical Center, Washington DC, USA.},
      year = {2014},
      volume = {5},
      pages = {534},
      url = {http://dx.doi.org/10.3389/fpsyg.2014.00534},
      doi = {http://doi.org/10.3389/fpsyg.2014.00534}
    }
    
    Fiandaca, M.S. & Federoff, H.J. Using viral-mediated gene delivery to model Parkinson's disease: do nonhuman primate investigations expand our understanding? 2014 Exp Neurol
    Vol. 256, pp. 117-125School: Department of Neurology, Georgetown University, Washington, D.C. 20007, USA; Department of Neuroscience, Georgetown University, Washington, D.C. 20007, USA. Electronic address: hjf8@georgetown.edu. 
    DOI URL 
    Abstract: In this review, we consider the use of nonhuman primate (NHP) models
    of Parkinson's disease (PD) produced using viral-mediated gene delivery
    and information they provide in comparison to other model systems
    in rodents and NHPs. To date, rodent and NHP PD models have found
    it difficult to fully recapitulate the human disorder and, therefore,
    provide little actual insight into disease progression. The viral-mediated
    gene delivery method for α-synuclein has been shown to produce a
    parkinsonian rodent and NHP. This novel viral-mediated gene transfer
    model in the NHP appears to provide a significant advance beyond
    neurotoxicant models, by more closely mimicking the more chronic
    time course of developed behavioral deterioration and neuropathology.
    Although we agree that the use of these novel methods inducing parkinsonian
    NHPs may provide relevant treatment insights, beyond those of more
    standard PD models, we remain cautious as to the preclinical models'
    ability to predict outcomes in human trials. In specific cases of
    certain novel medical therapeutics, therefore, we also consider the
    phase 0 clinical trial as offering an alternative to the currently
    non-predictive preclinical models, including those in the NHP.
    BibTeX:
    @article{Fiandaca2014b,
      author = {Fiandaca, Massimo S. and Federoff, Howard J.},
      title = {Using viral-mediated gene delivery to model Parkinson's disease: do nonhuman primate investigations expand our understanding?},
      journal = {Exp Neurol},
      school = {Department of Neurology, Georgetown University, Washington, D.C. 20007, USA; Department of Neuroscience, Georgetown University, Washington, D.C. 20007, USA. Electronic address: hjf8@georgetown.edu.},
      year = {2014},
      volume = {256},
      pages = {117--125},
      url = {http://dx.doi.org/10.1016/j.expneurol.2013.03.014},
      doi = {http://doi.org/10.1016/j.expneurol.2013.03.014}
    }
    
    Fiandaca, M.S., Kapogiannis, D., Mapstone, M., Boxer, A., Eitan, E., Schwartz, J.B., Abner, E.L., Petersen, R.C., Federoff, H.J., Miller, B.L. & Goetzl, E.J. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. 2014 Alzheimers DementSchool: Department of Medicine, UCSF Medical Center and the Jewish Home of San Francisco, San Francisco, CA, USA. Electronic address: edward.goetzl@ucsf.edu.  DOI URL 
    Abstract: Proteins pathogenic in Alzheimer's disease (AD) were extracted from
    neurally derived blood exosomes and quantified to develop biomarkers
    for the staging of sporadic AD.Blood exosomes obtained at one time-point
    from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16),
    and at two time-points from others (n = 24) when cognitively normal
    and 1 to 10 years later when diagnosed with AD were enriched for
    neural sources by immunoabsorption. AD-pathogenic exosomal proteins
    were extracted and quantified by enzyme-linked immunosorbent assays.Mean
    exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid
    ? 1-42 (A β1-42) for AD and levels of P-T181-tau and AΒ1-42 for FTD
    were significantly higher than for case-controls. Step-wise discriminant
    modeling incorporated P-T181-tau, P-S396-tau, and AΒ1-42 in AD, but
    only P-T181-tau in FTD. Classification of 96.4% of AD patients and
    87.5% of FTD patients was correct. In 24 AD patients, exosomal levels
    of P-S396-tau, P-T181-tau, and AΒ1-42 were significantly higher than
    for controls both 1 to 10 years before and when diagnosed with AD.Levels
    of P-S396-tau, P-T181-tau, and AΒ1-42 in extracts of neurally derived
    blood exosomes predict the development of AD up to 10 years before
    clinical onset.
    BibTeX:
    @article{Fiandaca2014,
      author = {Fiandaca, Massimo S. and Kapogiannis, Dimitrios and Mapstone, Mark and Boxer, Adam and Eitan, Erez and Schwartz, Janice B. and Abner, Erin L. and Petersen, Ronald C. and Federoff, Howard J. and Miller, Bruce L. and Goetzl, Edward J.},
      title = {Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study.},
      journal = {Alzheimers Dement},
      school = {Department of Medicine, UCSF Medical Center and the Jewish Home of San Francisco, San Francisco, CA, USA. Electronic address: edward.goetzl@ucsf.edu.},
      year = {2014},
      url = {http://dx.doi.org/10.1016/j.jalz.2014.06.008},
      doi = {http://doi.org/10.1016/j.jalz.2014.06.008}
    }
    
    Fiandaca, M.S., Mapstone, M.E., Cheema, A.K. & Federoff, H.J. The critical need for defining preclinical biomarkers in Alzheimer's disease. 2014 Alzheimers Dement
    Vol. 10(3 Suppl), pp. S196-S212School: Department of Neurology, Georgetown University Medical Center, Washington, DC, USA; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: hjf8@georgetown.edu. 
    DOI URL 
    Abstract: The increasing number of afflicted individuals with late-onset Alzheimer's
    disease (AD) poses significant emotional and financial burden on
    the world's population. Therapeutics designed to treat symptoms or
    alter the disease course have failed to make an impact, despite substantial
    investments by governments, pharmaceutical industry, and private
    donors. These failures in treatment efficacy have led many to believe
    that symptomatic disease, including both mild cognitive impairment
    (MCI) and AD, may be refractory to therapeutic intervention. The
    recent focus on biomarkers for defining the preclinical state of
    MCI/AD is in the hope of defining a therapeutic window in which the
    neural substrate remains responsive to treatment. The ability of
    biomarkers to adequately define the at-risk state may ultimately
    allow novel or repurposed therapeutic agents to finally achieve the
    disease-modifying status for AD. In this review, we examine current
    preclinical AD biomarkers and suggest how to generalize their use
    going forward.
    BibTeX:
    @article{Fiandaca2014a,
      author = {Fiandaca, Massimo S. and Mapstone, Mark E. and Cheema, Amrita K. and Federoff, Howard J.},
      title = {The critical need for defining preclinical biomarkers in Alzheimer's disease.},
      journal = {Alzheimers Dement},
      school = {Department of Neurology, Georgetown University Medical Center, Washington, DC, USA; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: hjf8@georgetown.edu.},
      year = {2014},
      volume = {10},
      number = {3 Suppl},
      pages = {S196--S212},
      url = {http://dx.doi.org/10.1016/j.jalz.2014.04.015},
      doi = {http://doi.org/10.1016/j.jalz.2014.04.015}
    }
    
    Fishburn, F.A., Norr, M.E., Medvedev, A.V. & Vaidya, C.J. Sensitivity of fNIRS to cognitive state and load. 2014 Front Hum Neurosci
    Vol. 8, pp. 76School: Department of Psychology, Georgetown University Washington, DC, USA ; Children's National Medical Center, Children's Research Institute Washington, DC, USA. 
    DOI URL 
    Abstract: Functional near-infrared spectroscopy (fNIRS) is an emerging low-cost
    noninvasive neuroimaging technique that measures cortical bloodflow.
    While fNIRS has gained interest as a potential alternative to fMRI
    for use with clinical and pediatric populations, it remains unclear
    whether fNIRS has the necessary sensitivity to serve as a replacement
    for fMRI. The present study set out to examine whether fNIRS has
    the sensitivity to detect linear changes in activation and functional
    connectivity in response to cognitive load, and functional connectivity
    changes when transitioning from a task-free resting state to a task.
    Sixteen young adult subjects were scanned with a continuous-wave
    fNIRS system during a 10-min resting-state scan followed by a letter
    n-back task with three load conditions. Five optical probes were
    placed over frontal and parietal cortices, covering bilateral dorsolateral
    PFC (dlPFC), bilateral ventrolateral PFC (vlPFC), frontopolar cortex
    (FP), and bilateral parietal cortex. Activation was found to scale
    linearly with working memory load in bilateral prefrontal cortex.
    Functional connectivity increased with increasing n-back loads for
    fronto-parietal, interhemispheric dlPFC, and local connections. Functional
    connectivity differed between the resting state scan and the n-back
    scan, with fronto-parietal connectivity greater during the n-back,
    and interhemispheric vlPFC connectivity greater during rest. These
    results demonstrate that fNIRS is sensitive to both cognitive load
    and state, suggesting that fNIRS is well-suited to explore the full
    complement of neuroimaging research questions and will serve as a
    viable alternative to fMRI.
    BibTeX:
    @article{Fishburn2014,
      author = {Fishburn, Frank A. and Norr, Megan E. and Medvedev, Andrei V. and Vaidya, Chandan J.},
      title = {Sensitivity of fNIRS to cognitive state and load.},
      journal = {Front Hum Neurosci},
      school = {Department of Psychology, Georgetown University Washington, DC, USA ; Children's National Medical Center, Children's Research Institute Washington, DC, USA.},
      year = {2014},
      volume = {8},
      pages = {76},
      url = {http://dx.doi.org/10.3389/fnhum.2014.00076},
      doi = {http://doi.org/10.3389/fnhum.2014.00076}
    }
    
    Forcelli, P.A., Palchik, G., Leath, T., DesJardin, J.T., Gale, K. & Malkova, L. Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys. 2014 Proc Natl Acad Sci U S A
    Vol. 111(11), pp. 4315-4320School: Department of Pharmacology and Physiology and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007. 
    DOI URL 
    Abstract: The hippocampus has a well-documented role for spatial navigation
    across species, but its role for spatial memory in nonnavigational
    tasks is uncertain. In particular, when monkeys are tested in tasks
    that do not require navigation, spatial memory seems unaffected by
    lesions of the hippocampus. However, the interpretation of these
    results is compromised by long-term compensatory adaptation occurring
    in the days and weeks after lesions. To test the hypothesis that
    hippocampus is necessary for nonnavigational spatial memory, we selected
    a technique that avoids long-term compensatory adaptation. We transiently
    disrupted hippocampal function acutely at the time of testing by
    microinfusion of the glutamate receptor antagonist kynurenate. Animals
    were tested on a self-ordered spatial memory task, the Hamilton Search
    Task. In the task, animals are presented with an array of eight boxes,
    each containing a food reinforcer; one box may be opened per trial,
    with trials separated by a delay. Only the spatial location of the
    boxes serves as a cue to solve the task. The optimal strategy is
    to open each box once without returning to previously visited locations.
    Transient inactivation of hippocampus reduced performance to chance
    levels in a delay-dependent manner. In contrast, no deficits were
    seen when boxes were marked with nonspatial cues (color). These results
    clearly document a role for hippocampus in nonnavigational spatial
    memory in macaques and demonstrate the efficacy of pharmacological
    inactivation of this structure in this species. Our data bring the
    role of the hippocampus in monkeys into alignment with the broader
    framework of hippocampal function.
    BibTeX:
    @article{Forcelli2014,
      author = {Forcelli, Patrick A. and Palchik, Guillermo and Leath, Taylor and DesJardin, Jacqueline T. and Gale, Karen and Malkova, Ludise},
      title = {Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys.},
      journal = {Proc Natl Acad Sci U S A},
      school = {Department of Pharmacology and Physiology and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007.},
      year = {2014},
      volume = {111},
      number = {11},
      pages = {4315--4320},
      url = {http://dx.doi.org/10.1073/pnas.1320562111},
      doi = {http://doi.org/10.1073/pnas.1320562111}
    }
    
    Giordano, J., Kulkarni, A. & Farwell, J. Deliver us from evil? The temptation, realities, and neuroethico-legal issues of employing assessment neurotechnologies in public safety initiatives. 2014 Theor Med Bioeth
    Vol. 35(1), pp. 73-89School: Neuroethics Studies Program, Edmund D. Pellegrino Center for Clinical Bioethics and Division of Integrative Physiology, Georgetown University, Washington, DC, USA, Jg353@georgetown.edu. 
    DOI URL 
    Abstract: In light of the recent events of terrorism and publicized cases of
    mass slayings and serial killings, there have been calls from the
    public and policy-makers alike for neuroscience and neurotechnology
    (neuroS/T) to be employed to intervene in ways that define and assess,
    if not prevent, such wanton acts of aggression and violence. Ongoing
    advancements in assessment neuroS/T have enabled heretofore unparalleled
    capabilities to evaluate the structure and function of the brain,
    yet each and all are constrained by certain technical and practical
    limitations. In this paper, we present an overview of the capabilities
    and constraints of current assessment neuroS/T, address neuro-ethical
    and legal issues fostered by the use and potential misuse of these
    approaches, and discuss how neuroethics may inform science and the
    law to guide right and sound applications of neuroS/T to "deliver
    us from evil" while not being led into temptations of ampliative
    claims and inapt use.
    BibTeX:
    @article{Giordano2014,
      author = {Giordano, James and Kulkarni, Anvita and Farwell, James},
      title = {Deliver us from evil? The temptation, realities, and neuroethico-legal issues of employing assessment neurotechnologies in public safety initiatives.},
      journal = {Theor Med Bioeth},
      school = {Neuroethics Studies Program, Edmund D. Pellegrino Center for Clinical Bioethics and Division of Integrative Physiology, Georgetown University, Washington, DC, USA, Jg353@georgetown.edu.},
      year = {2014},
      volume = {35},
      number = {1},
      pages = {73--89},
      url = {http://dx.doi.org/10.1007/s11017-014-9278-4},
      doi = {http://doi.org/10.1007/s11017-014-9278-4}
    }
    
    Gordon, E.M., Breeden, A.L., Bean, S.E. & Vaidya, C.J. Working memory-related changes in functional connectivity persist beyond task disengagement. 2014 Hum Brain Mapp
    Vol. 35(3), pp. 1004-1017School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC. 
    DOI URL 
    Abstract: We examined whether altered connectivity in functional networks during
    working memory performance persists following conclusion of that
    performance, into a subsequent resting state. We conducted functional
    magnetic resonance imaging (fMRI) in 50 young adults during an initial
    resting state, followed by an N-back working memory task and a subsequent
    resting state, in order to examine changes in functional connectivity
    within and between the default-mode network (DMN) and the task-positive
    network (TPN) across the three states. We found that alterations
    in connectivity observed during the N-back task persisted into the
    subsequent resting state within the TPN and between the DMN and TPN,
    but not within the DMN. Further, both speed of working memory performance
    and TPN connectivity strength during the N-back task predicted connectivity
    strength in the subsequent resting state. Finally, DMN connectivity
    measured before and during the N-back task predicted individual differences
    in self-reported inattentiveness, but this association was not found
    during the post-task resting state. Together, these findings have
    important implications for models of how the brain recovers following
    effortful cognition, as well as for experimental designs using resting
    and task scans.
    BibTeX:
    @article{Gordon2014,
      author = {Gordon, Evan M. and Breeden, Andrew L. and Bean, Stephanie E. and Vaidya, Chandan J.},
      title = {Working memory-related changes in functional connectivity persist beyond task disengagement.},
      journal = {Hum Brain Mapp},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC.},
      year = {2014},
      volume = {35},
      number = {3},
      pages = {1004--1017},
      url = {http://dx.doi.org/10.1002/hbm.22230},
      doi = {http://doi.org/10.1002/hbm.22230}
    }
    
    Green, A.E., Gray, J.R., Deyoung, C.G., Mhyre, T.R., Padilla, R., Dibattista, A.M. & William Rebeck, G. A combined effect of two Alzheimer's risk genes on medial temporal activity during executive attention in young adults. 2014 Neuropsychologia
    Vol. 56, pp. 1-8School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States. 
    DOI URL 
    Abstract: A recent history of failed clinical trials suggests that waiting until
    even the early stages of onset of Alzheimer's disease may be too
    late for effective treatment, pointing to the importance of early
    intervention in young people. Early intervention will require markers
    of Alzheimer's risk that track with genotype but are capable of responding
    to treatment. Here, we sought to identify a functional MRI signature
    of combined Alzheimer's risk imparted by two genetic risk factors.
    We used a task of executive attention during fMRI in participants
    genotyped for two Alzheimer's risk alleles: APOE-?4 and CLU-C. Executive
    attention is a sensitive indicator of the progression of Alzheimer's
    even in the early stages of mild cognitive impairment, but has not
    yet been investigated as a marker of Alzheimer's risk in young adults.
    Functional MRI revealed that APOE-?4 and CLU-C had an additive effect
    on brain activity such that increased combined genetic risk was associated
    with decreased brain activity during executive attention, including
    in the medial temporal lobe, a brain area affected early in Alzheimer's
    pathogenesis.
    BibTeX:
    @article{Green2014,
      author = {Green, Adam E. and Gray, Jeremy R. and Deyoung, Colin G. and Mhyre, Timothy R. and Padilla, Robert and Dibattista, Amanda M. and William Rebeck, G.},
      title = {A combined effect of two Alzheimer's risk genes on medial temporal activity during executive attention in young adults.},
      journal = {Neuropsychologia},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States.},
      year = {2014},
      volume = {56},
      pages = {1--8},
      url = {http://dx.doi.org/10.1016/j.neuropsychologia.2013.12.020},
      doi = {http://doi.org/10.1016/j.neuropsychologia.2013.12.020}
    }
    
    Grosser, S., Queenan, B.N., Lalchandani, R.R. & Vicini, S. Hilar somatostatin interneurons contribute to synchronized GABA activity in an in vitro epilepsy model. 2014 PLoS One
    Vol. 9(1), pp. e86250School: Department of Pharmacology and Physiology, Georgetown University, Washington, District of Columbia, United States of America ; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, United States of America. 
    DOI URL 
    Abstract: Epilepsy is a disorder characterized by excessive synchronized neural
    activity. The hippocampus and surrounding temporal lobe structures
    appear particularly sensitive to epileptiform activity. Somatostatin
    (SST)-positive interneurons within the hilar region have been suggested
    to gate hippocampal activity, and therefore may play a crucial role
    in the dysregulation of hippocampal activity. In this study, we examined
    SST interneuron activity in the in vitro 4-aminopyridine (4-AP) model
    of epilepsy. We employed a multi-disciplinary approach, combining
    extracellular multi-electrode array (MEA) recordings with patch-clamp
    recordings and optical imaging using a genetically encoded calcium
    sensor. We observed that hilar SST interneurons are strongly synchronized
    during 4-AP-induced local field potentials (LFPs), as assayed by
    Ca(2+) imaging as well as juxtacellular or intracellular recording.
    SST interneurons were particularly responsive to GABA-mediated LFPs
    that occurred in the absence of ionotropic glutamatergic transmission.
    Our results present evidence that the extensive synchronized activity
    of SST-expressing interneurons contribute to the generation of GABAergic
    LFPs in an in vitro model of temporal lobe seizures.
    BibTeX:
    @article{Grosser2014,
      author = {Grosser, Sabine and Queenan, Bridget N. and Lalchandani, Rupa R. and Vicini, Stefano},
      title = {Hilar somatostatin interneurons contribute to synchronized GABA activity in an in vitro epilepsy model.},
      journal = {PLoS One},
      school = {Department of Pharmacology and Physiology, Georgetown University, Washington, District of Columbia, United States of America ; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, United States of America.},
      year = {2014},
      volume = {9},
      number = {1},
      pages = {e86250},
      url = {http://dx.doi.org/10.1371/journal.pone.0086250},
      doi = {http://doi.org/10.1371/journal.pone.0086250}
    }
    
    Gutherz, S.B., Kulick, C.V., Soper, C., Kondratyev, A., Gale, K. & Forcelli, P.A. Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats. 2014 Epilepsy Behav
    Vol. 37C, pp. 265-269School: Department of Pharmacology and Physiology, Georgetown University, School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University, School of Medicine, Washington, DC 20007, USA. Electronic address: paf22@georgetown.edu. 
    DOI URL 
    Abstract: Phenobarbital is the most commonly utilized drug for the treatment
    of neonatal seizures. However, mounting preclinical evidence suggests
    that even brief exposure to phenobarbital in the neonatal period
    can induce neuronal apoptosis, alterations in synaptic development,
    and long-lasting changes in behavioral functions. In the present
    report, we treated neonatal rat pups with phenobarbital and evaluated
    behavior in adulthood. Pups were treated initially with a loading
    dose (80mg/kg) on postnatal day (P)7 and with a lower dose (40mg/kg)
    on P8 and P9. We examined sensorimotor gating (prepulse inhibition),
    passive avoidance, and conditioned place preference for cocaine when
    the animals reached adulthood. Consistent with our previous reports,
    we found that three days of neonatal exposure to phenobarbital significantly
    impaired prepulse inhibition compared with vehicle-exposed control
    animals. Using a step-though passive avoidance paradigm, we found
    that animals exposed to phenobarbital as neonates and tested as adults
    showed significant deficits in passive avoidance retention compared
    with matched controls, indicating impairment in associative memory
    and/or recall. Finally, we examined place preference conditioning
    in response to cocaine. Phenobarbital exposure did not alter the
    normal conditioned place preference associated with cocaine exposure.
    Our findings expand the profile of behavioral toxicity induced by
    phenobarbital.
    BibTeX:
    @article{Gutherz2014,
      author = {Gutherz, Samuel B. and Kulick, Catherine V. and Soper, Colin and Kondratyev, Alexei and Gale, Karen and Forcelli, Patrick A.},
      title = {Brief postnatal exposure to phenobarbital impairs passive avoidance learning and sensorimotor gating in rats.},
      journal = {Epilepsy Behav},
      school = {Department of Pharmacology and Physiology, Georgetown University, School of Medicine, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University, School of Medicine, Washington, DC 20007, USA. Electronic address: paf22@georgetown.edu.},
      year = {2014},
      volume = {37C},
      pages = {265--269},
      url = {http://dx.doi.org/10.1016/j.yebeh.2014.07.010},
      doi = {http://doi.org/10.1016/j.yebeh.2014.07.010}
    }
    
    Hebron, M., Chen, W., Miessau, M.J., Lonskaya, I. & Moussa, C.E.-H. Parkin reverses TDP-43-induced cell death and failure of amino acid homeostasis. 2014 J Neurochem
    Vol. 129(2), pp. 350-361School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: The E3 ubiquitin ligase Parkin plays a central role in the pathogenesis
    of many neurodegenerative diseases. Parkin promotes specific ubiquitination
    and affects the localization of transactivation response DNA-binding
    protein 43 (TDP-43), which controls the translation of thousands
    of mRNAs. Here we tested the effects of lentiviral Parkin and TDP-43
    expression on amino acid metabolism in the rat motor cortex using
    high frequency ??C NMR spectroscopy. TDP-43 expression increased
    glutamate levels, decreased the levels of other amino acids, including
    glutamine, aspartate, leucine and isoleucine, and impaired mitochondrial
    tricarboxylic acid cycle. TDP-43 induced lactate accumulation and
    altered the balance between excitatory (glutamate) and inhibitory
    (GABA) neurotransmitters. Parkin restored amino acid levels, neurotransmitter
    balance and tricarboxylic acid cycle metabolism, rescuing neurons
    from TDP-43-induced apoptotic death. Furthermore, TDP-43 expression
    led to an increase in 4E-BP levels, perhaps altering translational
    control and deregulating amino acid synthesis; while Parkin reversed
    the effects of TDP-43 on the 4E-BP signaling pathway. Taken together,
    these data suggest that Parkin may affect TDP-43 localization and
    mitigate its effects on 4E-BP signaling and loss of amino acid homeostasis.
    BibTeX:
    @article{Hebron2014,
      author = {Hebron, Michaeline and Chen, Wenqiang and Miessau, Matthew J. and Lonskaya, Irina and Moussa, Charbel E-H.},
      title = {Parkin reverses TDP-43-induced cell death and failure of amino acid homeostasis.},
      journal = {J Neurochem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA.},
      year = {2014},
      volume = {129},
      number = {2},
      pages = {350--361},
      url = {http://dx.doi.org/10.1111/jnc.12630},
      doi = {http://doi.org/10.1111/jnc.12630}
    }
    
    Hebron, M.L., Algarzae, N.K., Lonskaya, I. & Moussa, C. Fractalkine signaling and Tau hyper-phosphorylation are associated with autophagic alterations in lentiviral Tau and AΒ1-42 gene transfer models. 2014 Exp Neurol
    Vol. 251, pp. 127-138School: Department of Neuroscience, Georgetown University Medical Center, Washington D.C. 20007, USA. Electronic address: cem46@georgetown.edu. 
    DOI URL 
    Abstract: Tau hyper-phosphorylation (p-Tau) and neuro-inflammation are hallmarks
    of neurodegeneration. Previous findings suggest that microglial activation
    via CX3CL1 promotes p-Tau. We examined inflammation and autophagic
    p-Tau clearance in lentiviral Tau and mutant P301L expressing rats
    and used lentiviral AΒ1-42 to induce p-Tau. Lentiviral Tau or P301L
    expression significantly increased caspase-3 activity and TNF-?,
    but CX3CL1 was significantly higher in animals expressing Tau compared
    to P301L. Lentiviral AΒ1-42 induced p-Tau 4 weeks post-injection,
    and increased caspase-3 activation (8-fold) and TNF-? levels. Increased
    levels of ADAM-10/17 were also detected with p-Tau. IL-6 levels were
    increased but CX3CL1 did not change in the absence of p-Tau (2 weeks);
    however, p-Tau reversed these effects, which were associated with
    increased microglial activity. We observed changes in autophagic
    markers, including accumulation of autophagic vacuoles (AVs) and
    p-Tau accumulation in autophagosomes but not lysosomes, suggesting
    alteration of autophagy. Taken together, microglial activation may
    promote p-Tau independent of total Tau levels via CX3CL1 signaling,
    which seems to depend on interaction with inflammatory markers, mainly
    IL-6. The simultaneous change in autophagy and CX3CL1 signaling suggests
    communication between microglia and neurons, raising the possibility
    that accumulation of intraneuronal amyloid, due to lack of autophagic
    clearance, may lead microglia activation to promote p-Tau as a tag
    for phagocytic degradation.
    BibTeX:
    @article{Hebron2014a,
      author = {Hebron, Michaeline L. and Algarzae, Norah K. and Lonskaya, Irina and Moussa, Charbel},
      title = {Fractalkine signaling and Tau hyper-phosphorylation are associated with autophagic alterations in lentiviral Tau and AΒ1-42 gene transfer models.},
      journal = {Exp Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington D.C. 20007, USA. Electronic address: cem46@georgetown.edu.},
      year = {2014},
      volume = {251},
      pages = {127--138},
      url = {http://dx.doi.org/10.1016/j.expneurol.2013.01.009},
      doi = {http://doi.org/10.1016/j.expneurol.2013.01.009}
    }
    
    Hebron, M.L., Lonskaya, I., Olopade, P., Selby, S.T., Pagan, F. & Moussa, C.E.-H. Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in α-synucleinopathy. 2014 J Clin Cell Immunol
    Vol. 5, pp. 259School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington D.C., 20007, USA ; Neurorestoration Group, Movement Disorders Program, National Parkinson Foundation Center of Excellence, Georgetown University Hospital, Washington D.C., 20007, USA. 
    DOI URL 
    Abstract: Neuro-inflammation is common in α-synucleinopathies and Tauopathies;
    and evidence suggests a link between the tyrosine kinase Abl and
    neurodegeneration. Abl upregulates α-synuclein and promotes Tau hyper-phosphorylation
    (p-Tau), while Abl inhibitors facilitate autophagic clearance.A model
    of α-synucleinopathy harboring human mutant A53T α-synuclein and
    exhibits concomitant increase in murine p-Tau was used to determine
    the immunological response to Abl inhibition.Age-dependent alterations
    of brain immunity, including loss of IL-10 and decreased levels of
    IL-2 and IL-3 were observed in old A53T mice. Brain CCL2 and CCL5
    were decreased, but CX3CL1 remained constantly elevated. Young A53T
    mice exhibited differential systemic and central immune profiles
    in parallel with increased blood markers of adaptive immunity, suggesting
    an early systemic immune response. Tyrosine kinase inhibitors (TKIs),
    including nilotinib and bosutinib reduced brain and peripheral α-synuclein
    and p-Tau and modulated blood immunological responses. TKIs did not
    affect brain IL-10, but they changed the levels of all measured blood
    immune markers, except CX3CL1. TKIs altered microglia morphology
    and reduced the number of astrocyte and dendritic cells, suggesting
    beneficial regulation of microglia.These data indicate that tyrosine
    kinase inhibition affects neuro-inflammation via early changes of
    the peripheral immune profile, leading to modulation of the neuro-immune
    response to α-synuclein and p-Tau.
    BibTeX:
    @article{Hebron2014b,
      author = {Hebron, Michaeline L. and Lonskaya, Irina and Olopade, Paul and Selby, Sandra T. and Pagan, Fernando and Moussa, Charbel E-H.},
      title = {Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in α-synucleinopathy.},
      journal = {J Clin Cell Immunol},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington D.C., 20007, USA ; Neurorestoration Group, Movement Disorders Program, National Parkinson Foundation Center of Excellence, Georgetown University Hospital, Washington D.C., 20007, USA.},
      year = {2014},
      volume = {5},
      pages = {259},
      url = {http://dx.doi.org/10.4172/2155-9899.1000259},
      doi = {http://doi.org/10.4172/2155-9899.1000259}
    }
    
    Hung, C.P., Cui, D., Chen, Y.-P., Lin, C.-P. & Levine, M.R. Correlated activity supports efficient cortical processing. 2014 Front Comput Neurosci
    Vol. 8, pp. 171School: Department of Neuroscience, Georgetown University Washington, D.C., USA. 
    DOI URL 
    Abstract: Visual recognition is a computational challenge that is thought to
    occur via efficient coding. An important concept is sparseness, a
    measure of coding efficiency. The prevailing view is that sparseness
    supports efficiency by minimizing redundancy and correlations in
    spiking populations. Yet, we recently reported that "choristers",
    neurons that behave more similarly (have correlated stimulus preferences
    and spontaneous coincident spiking), carry more generalizable object
    information than uncorrelated neurons ("soloists") in macaque inferior
    temporal (IT) cortex. The rarity of choristers (as low as 6% of
    IT neurons) indicates that they were likely missed in previous studies.
    Here, we report that correlation strength is distinct from sparseness
    (choristers are not simply broadly tuned neurons), that choristers
    are located in non-granular output layers, and that correlated activity
    predicts human visual search efficiency. These counterintuitive results
    suggest that a redundant correlational structure supports efficient
    processing and behavior.
    BibTeX:
    @article{Hung2014,
      author = {Hung, Chou P. and Cui, Ding and Chen, Yueh-Peng and Lin, Chia-Pei and Levine, Matthew R.},
      title = {Correlated activity supports efficient cortical processing.},
      journal = {Front Comput Neurosci},
      school = {Department of Neuroscience, Georgetown University Washington, D.C., USA.},
      year = {2014},
      volume = {8},
      pages = {171},
      url = {http://dx.doi.org/10.3389/fncom.2014.00171},
      doi = {http://doi.org/10.3389/fncom.2014.00171}
    }
    
    Kikuchi, Y., Horwitz, B., Mishkin, M. & Rauschecker, J.P. Processing of harmonics in the lateral belt of macaque auditory cortex. 2014 Front Neurosci
    Vol. 8, pp. 204School: Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: Many speech sounds and animal vocalizations contain components, referred
    to as complex tones, that consist of a fundamental frequency (F0)
    and higher harmonics. In this study we examined single-unit activity
    recorded in the core (A1) and lateral belt (LB) areas of auditory
    cortex in two rhesus monkeys as they listened to pure tones and pitch-shifted
    conspecific vocalizations ("coos"). The latter consisted of complex-tone
    segments in which F0 was matched to a corresponding pure-tone stimulus.
    In both animals, neuronal latencies to pure-tone stimuli at the best
    frequency (BF) were ~10 to 15 ms longer in LB than in A1. This might
    be expected, since LB is considered to be at a hierarchically higher
    level than A1. On the other hand, the latency of LB responses to
    coos was ~10 to 20 ms shorter than to the corresponding pure-tone
    BF, suggesting facilitation in LB by the harmonics. This latency
    reduction by coos was not observed in A1, resulting in similar coo
    latencies in A1 and LB. Multi-peaked neurons were present in both
    A1 and LB; however, harmonically-related peaks were observed in LB
    for both early and late response components, whereas in A1 they were
    observed only for late components. Our results suggest that harmonic
    features, such as relationships between specific frequency intervals
    of communication calls, are processed at relatively early stages
    of the auditory cortical pathway, but preferentially in LB.
    BibTeX:
    @article{Kikuchi2014,
      author = {Kikuchi, Yukiko and Horwitz, Barry and Mishkin, Mortimer and Rauschecker, Josef P.},
      title = {Processing of harmonics in the lateral belt of macaque auditory cortex.},
      journal = {Front Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA.},
      year = {2014},
      volume = {8},
      pages = {204},
      url = {http://dx.doi.org/10.3389/fnins.2014.00204},
      doi = {http://doi.org/10.3389/fnins.2014.00204}
    }
    
    Kulick, C.V., Gutherz, S.B., Beck, V.C., Medvedeva, N., Soper, C. & Forcelli, P.A. Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-?-carboline-3-carboxylate) in neonatal rats. 2014 Eur J Pharmacol
    Vol. 743, pp. 63-68School: Department of Pharmacology and Physiology, Georgetown University, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University, School of Medicine, Washington, DC 20007, USA. Electronic address: paf22@georgetown.edu. 
    DOI URL 
    Abstract: Levetiracetam (LEV) and tiagabine (TGB) are utilized for the treatment
    of seizures, including neonatal seizures. However, relatively little
    is known about the preclinical therapeutic profile of these drugs
    during brain development. The relative paucity of information regarding
    these drugs in neonatal animals may be due to their unusual profile
    of anticonvulsant action in experimental models. LEV and TGB are
    without effect against seizures in several common screening models
    (e.g., the maximal electroshock test, maximal pentylenetetrazole
    seizures), instead showing preferential efficacy against models of
    partial seizures. We have recently described a method for reliably
    evoking partial seizures in neonatal animals by systemic administration
    of the chemoconvulsant, DMCM (Kulick et al., 2014, Eur. J. Pharmacol.,
    doi:10.1016/j.ejphar.2014.06.012). DMCM is a negative allosteric
    modulator of GABAA receptors, and offers a wide separation between
    doses required to evoke complex partial as compared to tonic-clonic
    seizures. Here we used DMCM to evaluate the effect of LEV and TGB
    against seizures in postnatal day (P) 10 rat pups. We compared the
    profile of LEV and TGB to that of phenobarbital (PB), the most widely
    utilized anticonvulsant in neonates. We found that LEV significantly
    protected against DMCM seizures when administered in doses of 10mg/kg
    and greater. TGB protected against DMCM-evoked seizures when administered
    in doses of 1mg/kg or greater. PB protected against DMCM-evoked seizures
    when administered in doses of 5mg/kg or greater. These data provide
    preclinical evidence for the efficacy of LEV and TGB in neonates
    and underscore the utility of DMCM for screening anticonvulsant action
    in neonatal animals.
    BibTeX:
    @article{Kulick2014,
      author = {Kulick, Catherine V. and Gutherz, Samuel B. and Beck, Veronica C. and Medvedeva, Natalia and Soper, Colin and Forcelli, Patrick A.},
      title = {Profile of anticonvulsant action of levetiracetam, tiagabine and phenobarbital against seizures evoked by DMCM (methyl-6,7-dimethoxy-4-ethyl-?-carboline-3-carboxylate) in neonatal rats.},
      journal = {Eur J Pharmacol},
      school = {Department of Pharmacology and Physiology, Georgetown University, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University, School of Medicine, Washington, DC 20007, USA. Electronic address: paf22@georgetown.edu.},
      year = {2014},
      volume = {743},
      pages = {63--68},
      url = {http://dx.doi.org/10.1016/j.ejphar.2014.09.016},
      doi = {http://doi.org/10.1016/j.ejphar.2014.09.016}
    }
    
    Kusmierek, P. & Rauschecker, J.P. Selectivity for space and time in early areas of the auditory dorsal stream in the rhesus monkey. 2014 J Neurophysiol
    Vol. 111(8), pp. 1671-1685School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. 
    DOI URL 
    Abstract: The respective roles of ventral and dorsal cortical processing streams
    are still under discussion in both vision and audition. We characterized
    neural responses in the caudal auditory belt cortex, an early dorsal
    stream region of the macaque. We found fast neural responses with
    elevated temporal precision as well as neurons selective to sound
    location. These populations were partly segregated: Neurons in a
    caudomedial area more precisely followed temporal stimulus structure
    but were less selective to spatial location. Response latencies in
    this area were even shorter than in primary auditory cortex. Neurons
    in a caudolateral area showed higher selectivity for sound source
    azimuth and elevation, but responses were slower and matching to
    temporal sound structure was poorer. In contrast to the primary area
    and other regions studied previously, latencies in the caudal belt
    neurons were not negatively correlated with best frequency. Our results
    suggest that two functional substreams may exist within the auditory
    dorsal stream.
    BibTeX:
    @article{Kusmierek2014,
      author = {Kusmierek, Pawel and Rauschecker, Josef P.},
      title = {Selectivity for space and time in early areas of the auditory dorsal stream in the rhesus monkey.},
      journal = {J Neurophysiol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia.},
      year = {2014},
      volume = {111},
      number = {8},
      pages = {1671--1685},
      url = {http://dx.doi.org/10.1152/jn.00436.2013},
      doi = {http://doi.org/10.1152/jn.00436.2013}
    }
    
    Lin, C.-P., Chen, Y.-P. & Hung, C.P. Tuning and spontaneous spike time synchrony share a common structure in macaque inferior temporal cortex. 2014 J Neurophysiol
    Vol. 112(4), pp. 856-869School: Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Neuroscience, Georgetown University, Washington, District of Columbia; and ch486@georgetown.edu. 
    DOI URL 
    Abstract: Investigating the relationship between tuning and spike timing is
    necessary to understand how neuronal populations in anterior visual
    cortex process complex stimuli. Are tuning and spontaneous spike
    time synchrony linked by a common spatial structure (do some cells
    covary more strongly, even in the absence of visual stimulation?),
    and what is the object coding capability of this structure? Here,
    we recorded from spiking populations in macaque inferior temporal
    (IT) cortex under neurolept anesthesia. We report that, although
    most nearby IT neurons are weakly correlated, neurons with more similar
    tuning are also more synchronized during spontaneous activity. This
    link between tuning and synchrony was not simply due to cell separation
    distance. Instead, it expands on previous reports that neurons along
    an IT penetration are tuned to similar but slightly different features.
    This constraint on possible population firing rate patterns was consistent
    across stimulus sets, including animate vs. inanimate object categories.
    A classifier trained on this structure was able to generalize category
    "read-out" to untrained objects using only a few dimensions (a few
    patterns of site weightings per electrode array). We suggest that
    tuning and spike synchrony are linked by a common spatial structure
    that is highly efficient for object representation.
    BibTeX:
    @article{Lin2014,
      author = {Lin, Chia-Pei and Chen, Yueh-Peng and Hung, Chou P.},
      title = {Tuning and spontaneous spike time synchrony share a common structure in macaque inferior temporal cortex.},
      journal = {J Neurophysiol},
      school = {Institute of Neuroscience and Brain Research Center, National Yang-Ming University, Taipei, Taiwan; Department of Neuroscience, Georgetown University, Washington, District of Columbia; and ch486@georgetown.edu.},
      year = {2014},
      volume = {112},
      number = {4},
      pages = {856--869},
      url = {http://dx.doi.org/10.1152/jn.00485.2013},
      doi = {http://doi.org/10.1152/jn.00485.2013}
    }
    
    Lonskaya, I., Hebron, M., Chen, W., Schachter, J. & Moussa, C. Tau deletion impairs intracellular ?-amyloid-42 clearance and leads to more extracellular plaque deposition in gene transfer models. 2014 Mol Neurodegener
    Vol. 9, pp. 46School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, 3970 Reservoir RD, Washington, DC 20057, USA. cem46@georgetown.edu. 
    DOI URL 
    Abstract: Tau is an axonal protein that binds to and regulates microtubule function.
    Hyper-phosphorylation of Tau reduces its binding to microtubules
    and it is associated with ?-amyloid deposition in Alzheimer's disease.
    Paradoxically, Tau reduction may prevent ?-amyloid pathology, raising
    the possibility that Tau mediates intracellular AΒ clearance. The
    current studies investigated the role of Tau in autophagic and proteasomal
    intracellular AΒ1-42 clearance and the subsequent effect on plaque
    deposition.Tau deletion impaired AΒ clearance via autophagy, but
    not the proteasome, while introduction of wild type human Tau into
    Tau-/- mice partially restored autophagic clearance of AΒ1-42, suggesting
    that exogenous Tau expression can support autophagic AΒ1-42 clearance.
    Tau deletion impaired autophagic flux and resulted in AΒ1-42 accumulation
    in pre-lysosomal autophagic vacuoles, affecting AΒ1-42 deposition
    into the lysosome. This autophagic defect was associated with decreased
    intracellular AΒ1-42 and increased plaque load in Tau-/- mice, which
    displayed less cell death. Nilotinib, an Abl tyrosine kinase inhibitor
    that promotes autophagic clearance mechanisms, reduced AΒ1-42 only
    when exogenous human Tau was expressed in Tau-/- mice.These studies
    demonstrate that Tau deletion affects intracellular AΒ1-42 clearance,
    leading to extracellular plaque.
    BibTeX:
    @article{Lonskaya2014a,
      author = {Lonskaya, Irina and Hebron, Michaeline and Chen, Wenqiang and Schachter, Joel and Moussa, Charbel},
      title = {Tau deletion impairs intracellular Beta-amyloid-42 clearance and leads to more extracellular plaque deposition in gene transfer models.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, 3970 Reservoir RD, Washington, DC 20057, USA. cem46@georgetown.edu.},
      year = {2014},
      volume = {9},
      pages = {46},
      url = {http://dx.doi.org/10.1186/1750-1326-9-46},
      doi = {http://doi.org/10.1186/1750-1326-9-46}
    }
    
    Lonskaya, I., Hebron, M.L., Desforges, N.M., Schachter, J.B. & Moussa, C.E.-H. Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance. 2014 J Mol Med (Berl)
    Vol. 92(4), pp. 373-386School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, 3970 Reservoir Rd, NW, TRB, Room WP26B, Washington, DC, 20057, USA. 
    DOI URL 
    Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder associated
    with amyloid accumulation and autophagic changes. Parkin is an E3
    ubiquitin ligase involved in proteasomal and autophagic clearance.
    We previously demonstrated decreased parkin solubility and interaction
    with the key autophagy enzyme beclin-1 in AD, but tyrosine kinase
    inhibition restored parkin-beclin-1 interaction. In the current studies,
    we determined the mechanisms of nilotinib-induced parkin-beclin-1
    interaction, which leads to amyloid clearance. Nilotinib increased
    endogenous parkin levels and ubiquitination, which may enhance parkin
    recycling via the proteasome, leading to increased activity and interaction
    with beclin-1. Parkin solubility was decreased and autophagy was
    altered in amyloid expressing mice, suggesting that amyloid stress
    affects parkin stability, leading to failure of protein clearance
    via the lysosome. Isolation of autophagic vacuoles revealed amyloid
    and parkin accumulation in autophagic compartments but nilotinib
    decreased insoluble parkin levels and facilitated amyloid deposition
    into lysosomes in wild type, but not parkin(-/-) mice, further underscoring
    an essential role for endogenous parkin in amyloid clearance. These
    results suggest that nilotinib boosts the autophagic machinery, leading
    to increased level of endogenous parkin that undergoes ubiquitination
    and interacts with beclin-1 to facilitate amyloid clearance. These
    data suggest that nilotinib-mediated autophagic changes may trigger
    parkin response via increased protein levels, providing a therapeutic
    strategy to reduce AΒ and Tau in AD.Parkin solubility (stability)
    is decreased in AD and APP transgenic mice. Nilotinib-induced autophagic
    changes increase endogenous parkin level. Increased parkin level
    leads to ubiquitination and proteasomal recycling. Re-cycling decreases
    insoluble parkin and increases parkin-beclin-1 interaction. Beclin-1-parkin
    interaction enhances amyloid clearance.
    BibTeX:
    @article{Lonskaya2014,
      author = {Lonskaya, Irina and Hebron, Michaeline L. and Desforges, Nicole M. and Schachter, Joel B. and Moussa, Charbel E-H.},
      title = {Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance.},
      journal = {J Mol Med (Berl)},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, 3970 Reservoir Rd, NW, TRB, Room WP26B, Washington, DC, 20057, USA.},
      year = {2014},
      volume = {92},
      number = {4},
      pages = {373--386},
      url = {http://dx.doi.org/10.1007/s00109-013-1112-3},
      doi = {http://doi.org/10.1007/s00109-013-1112-3}
    }
    
    Lum, J.A.G., Conti-Ramsden, G., Morgan, A.T. & Ullman, M.T. Procedural learning deficits in specific language impairment (SLI): a meta-analysis of serial reaction time task performance. 2014 Cortex
    Vol. 51, pp. 1-10School: Department of Neuroscience, Georgetown University, Washington, D.C., USA. 
    DOI URL 
    Abstract: Meta-analysis and meta-regression were used to evaluate whether evidence
    to date demonstrates deficits in procedural memory in individuals
    with specific language impairment (SLI), and to examine reasons for
    inconsistencies of findings across studies. The Procedural Deficit
    Hypothesis (PDH) proposes that SLI is largely explained by abnormal
    functioning of the frontal-basal ganglia circuits that support procedural
    memory. It has also been suggested that declarative memory can compensate
    for at least some of the problems observed in individuals with SLI.
    A number of studies have used Serial Reaction Time (SRT) tasks to
    investigate procedural learning in SLI. In this report, results from
    eight studies that collectively examined 186 participants with SLI
    and 203 typically-developing peers were submitted to a meta-analysis.
    The average mean effect size was .328 (CI95: .071, .584) and was
    significant. This suggests SLI is associated with impairments of
    procedural learning as measured by the SRT task. Differences among
    individual study effect sizes, examined with meta-regression, indicated
    that smaller effect sizes were found in studies with older participants,
    and in studies that had a larger number of trials on the SRT task.
    The contributions of age and SRT task characteristics to learning
    are discussed with respect to impaired and compensatory neural mechanisms
    in SLI.
    BibTeX:
    @article{Lum2014,
      author = {Lum, Jarrad A G. and Conti-Ramsden, Gina and Morgan, Angela T. and Ullman, Michael T.},
      title = {Procedural learning deficits in specific language impairment (SLI): a meta-analysis of serial reaction time task performance.},
      journal = {Cortex},
      school = {Department of Neuroscience, Georgetown University, Washington, D.C., USA.},
      year = {2014},
      volume = {51},
      pages = {1--10},
      url = {http://dx.doi.org/10.1016/j.cortex.2013.10.011},
      doi = {http://doi.org/10.1016/j.cortex.2013.10.011}
    }
    
    Mapstone, M., Cheema, A.K., Fiandaca, M.S., Zhong, X., Mhyre, T.R., MacArthur, L.H., Hall, W.J., Fisher, S.G., Peterson, D.R., Haley, J.M., Nazar, M.D., Rich, S.A., Berlau, D.J., Peltz, C.B., Tan, M.T., Kawas, C.H. & Federoff, H.J. Plasma phospholipids identify antecedent memory impairment in older adults. 2014 Nat Med
    Vol. 20(4), pp. 415-418School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: Alzheimer's disease causes a progressive dementia that currently affects
    over 35 million individuals worldwide and is expected to affect 115
    million by 2050 (ref. 1). There are no cures or disease-modifying
    therapies, and this may be due to our inability to detect the disease
    before it has progressed to produce evident memory loss and functional
    decline. Biomarkers of preclinical disease will be critical to the
    development of disease-modifying or even preventative therapies.
    Unfortunately, current biomarkers for early disease, including cerebrospinal
    fluid tau and amyloid-β levels, structural and functional magnetic
    resonance imaging and the recent use of brain amyloid imaging or
    inflammaging, are limited because they are either invasive, time-consuming
    or expensive. Blood-based biomarkers may be a more attractive option,
    but none can currently detect preclinical Alzheimer's disease with
    the required sensitivity and specificity. Herein, we describe our
    lipidomic approach to detecting preclinical Alzheimer's disease in
    a group of cognitively normal older adults. We discovered and validated
    a set of ten lipids from peripheral blood that predicted phenoconversion
    to either amnestic mild cognitive impairment or Alzheimer's disease
    within a 2-3 year timeframe with over 90% accuracy. This biomarker
    panel, reflecting cell membrane integrity, may be sensitive to early
    neurodegeneration of preclinical Alzheimer's disease.
    BibTeX:
    @article{Mapstone2014,
      author = {Mapstone, Mark and Cheema, Amrita K. and Fiandaca, Massimo S. and Zhong, Xiaogang and Mhyre, Timothy R. and MacArthur, Linda H. and Hall, William J. and Fisher, Susan G. and Peterson, Derick R. and Haley, James M. and Nazar, Michael D. and Rich, Steven A. and Berlau, Dan J. and Peltz, Carrie B. and Tan, Ming T. and Kawas, Claudia H. and Federoff, Howard J.},
      title = {Plasma phospholipids identify antecedent memory impairment in older adults.},
      journal = {Nat Med},
      school = { Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2014},
      volume = {20},
      number = {4},
      pages = {415--418},
      url = {http://dx.doi.org/10.1038/nm.3466},
      doi = {http://doi.org/10.1038/nm.3466}
    }
    
    Martin, B.S., Corbin, J.G. & Huntsman, M.M. Deficient tonic GABAergic conductance and synaptic balance in the fragile X syndrome amygdala. 2014 J Neurophysiol
    Vol. 112(4), pp. 890-902School: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences and Department of Pediatrics, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado molly.huntsman@ucdenver.edu. 
    DOI URL 
    Abstract: Fragile X syndrome (FXS) is the leading cause of inherited intellectual
    disability. Comorbidities of FXS such as autism are increasingly
    linked to imbalances in excitation and inhibition (E/I) as well as
    dysfunction in GABAergic transmission in a number of brain regions
    including the amygdala. However, the link between E/I imbalance and
    GABAergic transmission deficits in the FXS amygdala is poorly understood.
    Here we reveal that normal tonic GABAA receptor-mediated neurotransmission
    in principal neurons (PNs) of the basolateral amygdala (BLA) is comprised
    of both ?- and ?5-subunit-containing GABAA receptors. Furthermore,
    tonic GABAergic capacity is reduced in these neurons in the Fmr1
    knockout (KO) mouse model of FXS (1.5-fold total, 3-fold ?-subunit,
    and 2-fold ?5-subunit mediated) as indicated by application of gabazine
    (50 ?M), 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP, 1
    ?M), and ?5ia (1.5 ?M) in whole cell patch-clamp recordings. Moreover,
    ?5-containing tonic GABAA receptors appear to preferentially modulate
    nonsomatic compartments of BLA PNs. Examination of evoked feedforward
    synaptic transmission in these cells surprisingly revealed no differences
    in overall synaptic conductance or E/I balance between wild-type
    (WT) and Fmr1 KO mice. Instead, we observed altered feedforward kinetics
    in Fmr1 KO PNs that supports a subtle yet significant decrease in
    E/I balance at the peak of excitatory conductance. Blockade of ?5-subunit-containing
    GABAA receptors replicated this condition in WT PNs. Therefore, our
    data suggest that tonic GABAA receptor-mediated neurotransmission
    can modulate synaptic E/I balance and timing established by feedforward
    inhibition and thus may represent a therapeutic target to enhance
    amygdala function in FXS.
    BibTeX:
    @article{Martin2014,
      author = {Martin, Brandon S. and Corbin, Joshua G. and Huntsman, Molly M.},
      title = {Deficient tonic GABAergic conductance and synaptic balance in the fragile X syndrome amygdala.},
      journal = {J Neurophysiol},
      school = {Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences and Department of Pediatrics, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado molly.huntsman@ucdenver.edu.},
      year = {2014},
      volume = {112},
      number = {4},
      pages = {890--902},
      url = {http://dx.doi.org/10.1152/jn.00597.2013},
      doi = {http://doi.org/10.1152/jn.00597.2013}
    }
    
    McKee, J.L., Riesenhuber, M., Miller, E.K. & Freedman, D.J. Task dependence of visual and category representations in prefrontal and inferior temporal cortices. 2014 J Neurosci
    Vol. 34(48), pp. 16065-16075School: Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, dfreedman@uchicago.edu. 
    DOI URL 
    Abstract: Visual categorization is an essential perceptual and cognitive process
    for assigning behavioral significance to incoming stimuli. Categorization
    depends on sensory processing of stimulus features as well as flexible
    cognitive processing for classifying stimuli according to the current
    behavioral context. Neurophysiological studies suggest that the prefrontal
    cortex (PFC) and the inferior temporal cortex (ITC) are involved
    in visual shape categorization. However, their precise roles in the
    perceptual and cognitive aspects of the categorization process are
    unclear, as the two areas have not been directly compared during
    changing task contexts. To address this, we examined the impact of
    task relevance on categorization-related activity in PFC and ITC
    by recording from both areas as monkeys alternated between a shape
    categorization and passive viewing tasks. As monkeys viewed the same
    stimuli in both tasks, the impact of task relevance on encoding in
    each area could be compared. While both areas showed task-dependent
    modulations of neuronal activity, the patterns of results differed
    markedly. PFC, but not ITC, neurons showed a modest increase in firing
    rates when stimuli were task relevant. PFC also showed significantly
    stronger category selectivity during the task compared with passive
    viewing, while task-dependent modulations of category selectivity
    in ITC were weak and occurred with a long latency. Finally, both
    areas showed an enhancement of stimulus selectivity during the task
    compared with passive viewing. Together, this suggests that the ITC
    and PFC show differing degrees of task-dependent flexibility and
    are preferentially involved in the perceptual and cognitive aspects
    of the categorization process, respectively.
    BibTeX:
    @article{McKee2014,
      author = {McKee, Jillian L. and Riesenhuber, Maximilian and Miller, Earl K. and Freedman, David J.},
      title = {Task dependence of visual and category representations in prefrontal and inferior temporal cortices.},
      journal = {J Neurosci},
      school = {Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, dfreedman@uchicago.edu.},
      year = {2014},
      volume = {34},
      number = {48},
      pages = {16065--16075},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.1660-14.2014},
      doi = {http://doi.org/10.1523/JNEUROSCI.1660-14.2014}
    }
    
    Mocchetti, I., Bachis, A., Campbell, L.A. & Avdoshina, V. Implementing neuronal plasticity in NeuroAIDS: the experience of brain-derived neurotrophic factor and other neurotrophic factors. 2014 J Neuroimmune Pharmacol
    Vol. 9(2), pp. 80-91School: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, WP13 New Research Building, 3970 Reservoir Rd, NW, Washington, DC, 20057, USA, moccheti@georgetown.edu. 
    DOI URL 
    Abstract: Human immunodeficiency virus type-1 (HIV) causes mild or severe neurological
    problems, termed HIV-associated neurocognitive disorder (HAND), even
    when HIV patients receive antiretroviral therapy. Thus, novel adjunctive
    therapies are necessary to reduce or abolish the neurotoxic effect
    of HIV. However, new therapies require a better understanding of
    the molecular and cellular mechanisms of HIV-induced neurotoxicity.
    HAND subjects are characterized by being profoundly depressed, and
    they experience deficits in memory, learning and movements. Experimental
    evidence has also shown that HIV reduces neurogenesis. These deficits
    resemble those occurring in premature brain aging or in a brain with
    impaired neural repair properties. Thus, it appears that HIV diminishes
    neuronal survival, along with reduced neuronal connections. These
    two phenomena should not occur in the adult and developing brain
    when synaptic plasticity is promoted by neurotrophic factors, polypeptides
    that are present in adult synapses. This review will outline experimental
    evidence as well as present emerging concepts for the use of neurotrophic
    factors and in particular brain-derived neurotrophic factor as an
    adjunct therapy to prevent HIV-mediated neuronal degeneration and
    restore the loss of synaptic connections.
    BibTeX:
    @article{Mocchetti2014,
      author = {Mocchetti, Italo and Bachis, Alessia and Campbell, Lee A. and Avdoshina, Valeriya},
      title = {Implementing neuronal plasticity in NeuroAIDS: the experience of brain-derived neurotrophic factor and other neurotrophic factors.},
      journal = {J Neuroimmune Pharmacol},
      school = {Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, WP13 New Research Building, 3970 Reservoir Rd, NW, Washington, DC, 20057, USA, moccheti@georgetown.edu.},
      year = {2014},
      volume = {9},
      number = {2},
      pages = {80--91},
      url = {http://dx.doi.org/10.1007/s11481-013-9488-y},
      doi = {http://doi.org/10.1007/s11481-013-9488-y}
    }
    
    N'Gouemo, P. BKCa channel dysfunction in neurological diseases. 2014 Front Physiol
    Vol. 5, pp. 373School: Department of Pediatrics and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: The large conductance, Ca(2+)-activated K(+) channels (BKCa, KCa1.1)
    are expressed in various brain neurons where they play important
    roles in regulating action potential duration, firing frequency and
    neurotransmitter release. Membrane potential depolarization and rising
    levels of intracellular Ca(2+) gated BKCa channels, which in turn
    results in an outward K(+) flux that re/hyperpolarizes the membrane.
    The sensitivity of BKCa channels to Ca(2+) provides an important
    negative-feedback system for Ca(2+) entry into brain neurons and
    suppresses repetitive firing. Thus, BKCa channel loss-of-function
    gives rise to neuronal hyperexcitability, which can lead to seizures.
    Evidence also indicates that BKCa channels can facilitate high-frequency
    firing (gain-of-function) in some brain neurons. Interestingly, both
    gain-of-function and loss-of-function mutations of genes encoding
    for various BKCa channel subunits have been associated with the development
    of neuronal excitability disorders, such as seizure disorders. The
    role of BKCa channels in the etiology of some neurological diseases
    raises the possibility that these channels can be used as molecular
    targets to prevent and suppress disease phenotypes.
    BibTeX:
    @article{NGouemo2014,
      author = {N'Gouemo, Prosper},
      title = {BKCa channel dysfunction in neurological diseases.},
      journal = {Front Physiol},
      school = {Department of Pediatrics and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA.},
      year = {2014},
      volume = {5},
      pages = {373},
      url = {http://dx.doi.org/10.3389/fphys.2014.00373},
      doi = {http://doi.org/10.3389/fphys.2014.00373}
    }
    
    Nwabuisi-Heath, E., Rebeck, G.W., Ladu, M.J. & Yu, C. ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro. 2014 ASN Neuro
    Vol. 6(1), pp. e00134School: *Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, U.S.A. 
    DOI URL 
    Abstract: The ?4 allele of the gene that encodes apolipoprotein E (APOE4) is
    the greatest genetic risk factor for Alzheimer's disease (AD), while
    APOE2 reduces AD risk, compared to APOE3. The mechanism(s) underlying
    the effects of APOE on AD pathology remains unclear. In vivo, dendritic
    spine density is lower in APOE4-targeted replacement (APOE-TR) mice
    compared with APOE2- and APOE3-TR mice. To investigate whether this
    apoE4-induced decrease in spine density results from alterations
    in the formation or the loss of dendritic spines, the effects of
    neuron age and apoE isoform on the total number and subclasses of
    spines were examined in long-term wild-type neurons co-cultured with
    glia from APOE2-, APOE3- and APOE4-TR mice. Dendritic spine density
    and maturation were evaluated by immunocytochemistry via the presence
    of drebrin (an actin-binding protein) with GluN1 (NMDA receptor subunit)
    and GluA2 (AMPA receptor subunit) clusters. ApoE isoform effects
    were analyzed via a method previously established that identifies
    phases of spine formation (day-in-vitro, DIV10-18), maintenance (DIV18-21)
    and loss (DIV21-26). In the formation phase, apoE4 delayed total
    spine formation. During the maintenance phase, the density of GluN1+GluA2
    spines did not change with apoE2, while the density of these spines
    decreased with apoE4 compared to apoE3, primarily due to the loss
    of GluA2 in spines. During the loss phase, total spine density was
    lower in neurons with apoE4 compared to apoE3. Thus, apoE4 delays
    total spine formation and may induce early synaptic dysfunction via
    impaired regulation of GluA2 in spines.
    BibTeX:
    @article{Nwabuisi-Heath2014,
      author = {Nwabuisi-Heath, Evelyn and Rebeck, G William and Ladu, Mary Jo and Yu, Chunjiang},
      title = {ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro.},
      journal = {ASN Neuro},
      school = {*Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, U.S.A.},
      year = {2014},
      volume = {6},
      number = {1},
      pages = {e00134},
      url = {http://dx.doi.org/10.1042/AN20130043},
      doi = {http://doi.org/10.1042/AN20130043}
    }
    
    Partridge, J.G., Lewin, A.E., Yasko, J.R. & Vicini, S. Contrasting actions of group I metabotropic glutamate receptors in distinct mouse striatal neurones. 2014 J Physiol
    Vol. 592(Pt 13), pp. 2721-2733School: Department of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, 20007, USA Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC, 20007, USA. 
    DOI URL 
    Abstract: In mouse striatum, metabotropic glutamate receptor (mGluR) activation
    leads to several modulatory effects in synaptic transmission. These
    effects range from dampening of glutamate release from excitatory
    terminals to depolarization of divergent classes of interneurones.
    We compared the action of group I mGluR activation on several populations
    of striatal neurones using a combination of genetic identification,
    electrophysiology, and Ca(2+) imaging techniques. Patch-clamp recordings
    from spiny projection neurones (SPNs) and various interneurone populations
    demonstrated that the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine
    (DHPG) robustly depolarizes several interneurone classes that form
    GABAergic synapses onto SPNs. We further utilized the genetic reporter
    mouse strain Ai38, which expresses the calcium indicator protein
    GCaMP3 in a Cre-dependent manner. Breeding Ai38 mice with various
    neurone selective, promoter-driven Cre recombinase mice resulted
    in GCaMP3 expression in defined cell populations in striatum. Consistent
    with our electrophysiological findings, group I agonist applications
    increased intracellular levels of calcium ([Ca(2+)]i) in all interneurone
    populations tested. We also found that acute DHPG application evoked
    a transient, rapid increase in [Ca(2+)]i from only a small percentage
    of identifiable SPNs. Surprisingly, this fast [Ca(2+)]i response
    exhibited a robust enhancement or sensitization, in a calcium-dependent
    fashion. Following several procedures to increase [Ca(2+)]i, the
    vast majority of SPNs responded with rapid changes in [Ca(2+)]i to
    mGluR agonists in a time-dependent fashion. These findings extend
    our understanding on group I mGluR influence of striatal output via
    powerful, local GABAergic connections in addition to [Ca(2+)]i dynamics
    that impact on activity or spike-timing-dependent forms of synaptic
    plasticity.
    BibTeX:
    @article{Partridge2014,
      author = {Partridge, John G. and Lewin, Amanda E. and Yasko, Jessica R. and Vicini, Stefano},
      title = {Contrasting actions of group I metabotropic glutamate receptors in distinct mouse striatal neurones.},
      journal = {J Physiol},
      school = {Department of Pharmacology and Physiology, Georgetown University School of Medicine, Washington, DC, 20007, USA Interdisciplinary Program in Neuroscience, Georgetown University School of Medicine, Washington, DC, 20007, USA.},
      year = {2014},
      volume = {592},
      number = {Pt 13},
      pages = {2721--2733},
      url = {http://dx.doi.org/10.1113/jphysiol.2014.272773},
      doi = {http://doi.org/10.1113/jphysiol.2014.272773}
    }
    
    Passeri, E., Mocchetti, I. & Moussa, C. Is Human Immunodeficiency Virus-mediated Dementia an Autophagic Defect that Leads to Neurodegeneration? 2014 CNS Neurol Disord Drug TargetsSchool: Georgetown University Medical Center, Department of Neuroscience, NRB WP13, 3970 Reservoir Rd, NW, Washington, DC 20057 USA. moccheti@georgetown.edu.   
    Abstract: Autophagy is a cellular process that mediates selective degradation
    of cellular components in lysosomes. Autophagy may protect against
    neuronal apoptosis, which is induced in a number of neurodegenerative
    diseases. Thus, compounds that modulate autophagy could be beneficial
    to treat neurological disorders characterized by apoptosis such as
    Parkinson's and Alzheimer's diseases, as well as human-immunodeficiency
    virus-dementia complex. In this paper, we review new and old evidence
    on the role of autophagy in neuronal cell survival and we present
    evidence that human-immunodeficiency virus may have adapted strategies
    to alter autophagic pathways in neurons. Moreover, we discuss the
    usefulness of drugs that facilitate autophagic clearance of proteins
    that are associated with neurodegeneration.
    BibTeX:
    @article{Passeri2014,
      author = {Passeri, E. and Mocchetti, I. and Moussa, C.},
      title = {Is Human Immunodeficiency Virus-mediated Dementia an Autophagic Defect that Leads to Neurodegeneration?},
      journal = {CNS Neurol Disord Drug Targets},
      school = {Georgetown University Medical Center, Department of Neuroscience, NRB WP13, 3970 Reservoir Rd, NW, Washington, DC 20057 USA. moccheti@georgetown.edu.},
      year = {2014}
    }
    
    Rauschecker, J.P. Is there a tape recorder in your head? How the brain stores and retrieves musical melodies. 2014 Front Syst Neurosci
    Vol. 8, pp. 149School: Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA ; Institute for Advanced Studies, Technical University Munich Garching, Germany. 
    DOI URL 
    Abstract: Music consists of strings of sound that vary over time. Technical
    devices, such as tape recorders, store musical melodies by transcribing
    event times of temporal sequences into consecutive locations on the
    storage medium. Playback occurs by reading out the stored information
    in the same sequence. However, it is unclear how the brain stores
    and retrieves auditory sequences. Neurons in the anterior lateral
    belt of auditory cortex are sensitive to the combination of sound
    features in time, but the integration time of these neurons is not
    sufficient to store longer sequences that stretch over several seconds,
    minutes or more. Functional imaging studies in humans provide evidence
    that music is stored instead within the auditory dorsal stream, including
    premotor and prefrontal areas. In monkeys, these areas are the substrate
    for learning of motor sequences. It appears, therefore, that the
    auditory dorsal stream transforms musical into motor sequence information
    and vice versa, realizing what are known as forward and inverse models.
    The basal ganglia and the cerebellum are involved in setting up the
    sensorimotor associations, translating timing information into spatial
    codes and back again.
    BibTeX:
    @article{Rauschecker2014,
      author = {Rauschecker, Josef P.},
      title = {Is there a tape recorder in your head? How the brain stores and retrieves musical melodies.},
      journal = {Front Syst Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA ; Institute for Advanced Studies, Technical University Munich Garching, Germany.},
      year = {2014},
      volume = {8},
      pages = {149},
      url = {http://dx.doi.org/10.3389/fnsys.2014.00149},
      doi = {http://doi.org/10.3389/fnsys.2014.00149}
    }
    
    Renier, L., De Volder, A.G. & Rauschecker, J.P. Cortical plasticity and preserved function in early blindness. 2014 Neurosci Biobehav Rev
    Vol. 41, pp. 53-63School: Laboratory for Integrative Neuroscience and Cognition; Department of Neuroscience; Georgetown University, Medical Center; 3970 Reservoir Road, NW, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: The "neural Darwinism" theory predicts that when one sensory modality
    is lacking, as in congenital blindness, the target structures are
    taken over by the afferent inputs from other senses that will promote
    and control their functional maturation (Edelman, 1993). This view
    receives support from both cross-modal plasticity experiments in
    animal models and functional imaging studies in man, which are presented
    here.
    BibTeX:
    @article{Renier2014,
      author = {Renier, Laurent and De Volder, Anne G. and Rauschecker, Josef P.},
      title = {Cortical plasticity and preserved function in early blindness.},
      journal = {Neurosci Biobehav Rev},
      school = {Laboratory for Integrative Neuroscience and Cognition; Department of Neuroscience; Georgetown University, Medical Center; 3970 Reservoir Road, NW, Washington, DC 20007, USA.},
      year = {2014},
      volume = {41},
      pages = {53--63},
      url = {http://dx.doi.org/10.1016/j.neubiorev.2013.01.025},
      doi = {http://doi.org/10.1016/j.neubiorev.2013.01.025}
    }
    
    Rodriguez, G.A., Tai, L.M., LaDu, M.J. & Rebeck, G.W. Human APOE4 increases microglia reactivity at AΒ plaques in a mouse model of AΒ deposition. 2014 J Neuroinflammation
    Vol. 11, pp. 111School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW Washington, DC 20057, USA. gwr2@georgetown.edu. 
    DOI URL 
    Abstract: Having the apolipoprotein E4 (APOE-?4) allele is the strongest genetic
    risk factor for the development of Alzheimer's disease (AD). Accumulation
    of amyloid beta (AΒ) in the brain is influenced by APOE genotype.
    Transgenic mice co-expressing five familial AD mutations (5xFAD)
    in the presence of human APOE alleles (?2, ?3 or ?4) exhibit APOE
    genotype-specific differences in early AΒ accumulation, suggesting
    an interaction between APOE and AD pathology. Whether APOE genotype
    affects AΒ-plaque-associated neuroinflammation remains unclear. In
    the current study, we address the role of APOE genotype on AΒ-associated
    microglial reactivity in the EFAD transgenic mouse model.We analyzed
    AΒ-induced glial activation in the brains of 6-month-old EFAD transgenic
    mice (E2FAD, E3FAD and E4FAD). Region-specific morphological profiles
    of AΒ plaques in EFAD brain sections were compared using immunofluorescence
    staining. We then determined the degree of glial activation in sites
    of AΒ deposition while comparing levels of the inflammatory cytokine
    Interleukin-1? (IL-1?) by ELISA. Finally, we quantified parameters
    of AΒ-associated microglial reactivity using double-stained EFAD
    brain sections.Characterization of AΒ plaques revealed there were
    larger and more intensely stained plaques in E4FAD mice relative
    to E2FAD and E3FAD mice. E4FAD mice also had a greater percentage
    of compact plaques in the subiculum than E3FAD mice. Reactive microglia
    and dystrophic astrocytes were prominent in EFAD brains, and primarily
    localized to two sites of significant AΒ deposition: the subiculum
    and deep layers of the cortex. Cortical levels of IL-1? were nearly
    twofold greater in E4FAD mice relative to E3FAD mice. To control
    for differences in levels of AΒ in the different EFAD mice, we analyzed
    the microglia within domains of specific AΒ deposits. Morphometric
    analyses revealed increased measures of microglial reactivity in
    E4FAD mice, including greater dystrophy, increased fluorescence intensity
    and a higher density of reactive cells surrounding cortical plaques,
    than in E3FAD mice.In addition to altering morphological profiles
    of AΒ deposition, APOE genotype influences AΒ-induced glial activation
    in the adult EFAD cortex. These data support a role for APOE in modulating
    AΒ-induced neuroinflammatory responses in AD progression, and support
    the use of EFAD mice as a suitable model for mechanistic studies
    of AΒ-associated neuroinflammation.
    BibTeX:
    @article{Rodriguez2014,
      author = {Rodriguez, Gustavo A. and Tai, Leon M. and LaDu, Mary Jo and Rebeck, G William},
      title = {Human APOE4 increases microglia reactivity at AΒ plaques in a mouse model of AΒ deposition.},
      journal = {J Neuroinflammation},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW Washington, DC 20057, USA. gwr2@georgetown.edu.},
      year = {2014},
      volume = {11},
      pages = {111},
      url = {http://dx.doi.org/10.1186/1742-2094-11-111},
      doi = {http://doi.org/10.1186/1742-2094-11-111}
    }
    
    Rozzi, S.J., Borelli, G., Ryan, K., Steiner, J.P., Reglodi, D., Mocchetti, I. & Avdoshina, V. PACAP27 is Protective Against Tat-Induced Neurotoxicity. 2014 J Mol NeurosciSchool: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.  DOI URL 
    Abstract: Human immunodeficiency virus type-1 (HIV) infection of the central
    nervous system promotes neuronal injury and apoptosis that culminate
    in HIV-associated neurocognitive disorders (HAND). Viral proteins,
    such as transactivator of transcription (Tat), have emerged as leading
    candidates to explain HIV-mediated neurotoxicity, though the mechanism
    remains unclear. To determine the effects of Tat, rat cortical neurons
    were exposed to nanomolar concentrations of Tat for various time
    points. Within a few hours, Tat induced the production of reactive
    oxygen species (ROS), and other indices of mitochondrial destabilization.
    In addition, we observed a significant induction of DNA double-strand
    breaks (DSBs) by Tat. We next investigated the neuroprotective activity
    of the pituitary adenylate cyclase-activating polypeptide 27 (PACAP27)
    against these cardinal features of Tat-induced neurodegeneration.
    PACAP27 (100 nM) inhibited all Tat-mediated toxic effects including
    DNA DSBs. Importantly, PACAP27 prevented the induction of neuronal
    loss induced by Tat. The neuroprotective effect of PACAP27 is correlated
    with its ability to release the anti-apoptotic chemokine CCL5. Our
    data support a mechanism of Tat neurotoxicity in which Tat induces
    mitochondrial destabilization, thus increasing the release of ROS,
    which causes DNA DSBs leading to cell death. PACAP27, through CCL5,
    mitigates the effects of Tat-induced neuronal dysfunction, suggesting
    that PACAP27 could be a new strategy for an adjunct therapy against
    HIV-associated neurocognitive disorders.
    BibTeX:
    @article{Rozzi2014,
      author = {Rozzi, Summer J. and Borelli, Giulia and Ryan, Kerry and Steiner, Joseph P. and Reglodi, Dora and Mocchetti, Italo and Avdoshina, Valeriya},
      title = {PACAP27 is Protective Against Tat-Induced Neurotoxicity.},
      journal = {J Mol Neurosci},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.},
      year = {2014},
      url = {http://dx.doi.org/10.1007/s12031-014-0273-z},
      doi = {http://doi.org/10.1007/s12031-014-0273-z}
    }
    
    Savolainen, M.H., Richie, C.T., Harvey, B.K., M?nnist?, P.T., Maguire-Zeiss, K.A. & My?h?nen, T.T. The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse. 2014 Neurobiol Dis
    Vol. 68, pp. 1-15School: timo.myohanen@helsinki.fi. 
    DOI URL 
    Abstract: The misfolding and aggregation of α-synuclein (aSyn) eventually lead
    to an accumulation of toxic forms that disturb normal neuronal function
    and result in cell death. aSyn rich inclusions are seen in Parkinson's
    disease, dementia with Lewy bodies and other synucleinopathies. Prolyl
    oligopeptidase (PREP) can accelerate the aggregation process of aSyn
    and the inhibition of PREP leads to a decreased amount of aggregated
    aSyn in cell models and in aSyn transgenic mice. In this study, we
    investigated the effect of 5- and 28-day PREP inhibitor (KYP-2047)
    treatments on a mouse strain carrying a point mutation in the aSyn
    coding gene. Following PREP inhibition, we found a decrease in high
    molecular-weight oligomeric aSyn and a concomitant increase in the
    amount of the autophagosome marker, LC3BII, suggesting enhanced macroautophagy
    (autophagy) and aSyn clearance by KYP-2047. Moreover, 28-day treatment
    with KYP-2047 caused significant increases in striatal dopamine levels.
    In cell culture, overexpression of PREP reduced the autophagy. Furthermore,
    the inhibition of PREP normalized the changes on autophagy markers
    (LC3BII and p62) caused by an autophagy inhibition or aSyn overexpression,
    and induced the expression of beclin 1, a positive regulator of autophagy.
    Taken together, our results suggest that PREP inhibition accelerates
    the clearance of protein aggregates via increased autophagy and thus
    normalizes the cell functions in vivo and in vitro. Therefore, PREP
    inhibition may have future potential in the treatment of synucleinopathies.
    BibTeX:
    @article{Savolainen2014,
      author = {Savolainen, Mari H. and Richie, Christopher T. and Harvey, Brandon K. and M?nnist?, Pekka T. and Maguire-Zeiss, Kathleen A. and My?h?nen, Timo T.},
      title = {The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse.},
      journal = {Neurobiol Dis},
      school = { timo.myohanen@helsinki.fi.},
      year = {2014},
      volume = {68},
      pages = {1--15},
      url = {http://dx.doi.org/10.1016/j.nbd.2014.04.003},
      doi = {http://doi.org/10.1016/j.nbd.2014.04.003}
    }
    
    Seydell-Greenwald, A., Greenberg, A.S. & Rauschecker, J.P. Are you listening? Brain activation associated with sustained nonspatial auditory attention in the presence and absence of stimulation. 2014 Hum Brain Mapp
    Vol. 35(5), pp. 2233-2252School: Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington DC, 20007. 
    DOI URL 
    Abstract: Neuroimaging studies investigating the voluntary (top-down) control
    of attention largely agree that this process recruits several frontal
    and parietal brain regions. Since most studies used attention tasks
    requiring several higher-order cognitive functions (e.g. working
    memory, semantic processing, temporal integration, spatial orienting)
    as well as different attentional mechanisms (attention shifting,
    distractor filtering), it is unclear what exactly the observed frontoparietal
    activations reflect. The present functional magnetic resonance imaging
    study investigated, within the same participants, signal changes
    in (1) a "Simple Attention" task in which participants attended to
    a single melody, (2) a "Selective Attention" task in which they simultaneously
    ignored another melody, and (3) a "Beep Monitoring" task in which
    participants listened in silence for a faint beep. Compared to resting
    conditions with identical stimulation, all tasks produced robust
    activation increases in auditory cortex, cross-modal inhibition in
    visual and somatosensory cortex, and decreases in the default mode
    network, indicating that participants were indeed focusing their
    attention on the auditory domain. However, signal increases in frontal
    and parietal brain areas were only observed for tasks 1 and 2, but
    completely absent for task 3. These results lead to the following
    conclusions: under most conditions, frontoparietal activations are
    crucial for attention since they subserve higher-order cognitive
    functions inherently related to attention. However, under circumstances
    that minimize other demands, nonspatial auditory attention in the
    absence of stimulation can be maintained without concurrent frontal
    or parietal activations.
    BibTeX:
    @article{Seydell-Greenwald2014a,
      author = {Seydell-Greenwald, Anna and Greenberg, Adam S. and Rauschecker, Josef P.},
      title = {Are you listening? Brain activation associated with sustained nonspatial auditory attention in the presence and absence of stimulation.},
      journal = {Hum Brain Mapp},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington DC, 20007.},
      year = {2014},
      volume = {35},
      number = {5},
      pages = {2233--2252},
      url = {http://dx.doi.org/10.1002/hbm.22323},
      doi = {http://doi.org/10.1002/hbm.22323}
    }
    
    Seydell-Greenwald, A., Raven, E.P., Leaver, A.M., Turesky, T.K. & Rauschecker, J.P. Diffusion imaging of auditory and auditory-limbic connectivity in tinnitus: preliminary evidence and methodological challenges. 2014 Neural Plast
    Vol. 2014, pp. 145943School: Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, New Research Building, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Subjective tinnitus, or "ringing in the ears," is perceived by 10
    to 15 percent of the adult population and causes significant suffering
    in a subset of patients. While it was originally thought of as a
    purely auditory phenomenon, there is increasing evidence that the
    limbic system influences whether and how tinnitus is perceived, far
    beyond merely determining the patient's emotional reaction to the
    phantom sound. Based on functional imaging and electrophysiological
    data, recent articles frame tinnitus as a "network problem" arising
    from abnormalities in auditory-limbic interactions. Diffusion-weighted
    magnetic resonance imaging is a noninvasive method for investigating
    anatomical connections in vivo. It thus has the potential to provide
    anatomical evidence for the proposed changes in auditory-limbic connectivity.
    However, the few diffusion imaging studies of tinnitus performed
    to date have inconsistent results. In the present paper, we briefly
    summarize the results of previous studies, aiming to reconcile their
    results. After detailing analysis methods, we then report findings
    from a new dataset. We conclude that while there is some evidence
    for tinnitus-related increases in auditory and auditory-limbic connectivity
    that counteract hearing-loss related decreases in auditory connectivity,
    these results should be considered preliminary until several technical
    challenges have been overcome.
    BibTeX:
    @article{Seydell-Greenwald2014,
      author = {Seydell-Greenwald, Anna and Raven, Erika P. and Leaver, Amber M. and Turesky, Ted K. and Rauschecker, Josef P.},
      title = {Diffusion imaging of auditory and auditory-limbic connectivity in tinnitus: preliminary evidence and methodological challenges.},
      journal = {Neural Plast},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, New Research Building, Washington, DC 20007, USA.},
      year = {2014},
      volume = {2014},
      pages = {145943},
      url = {http://dx.doi.org/10.1155/2014/145943},
      doi = {http://doi.org/10.1155/2014/145943}
    }
    
    Shook, J.R. & Giordano, J. A principled and cosmopolitan neuroethics: considerations for international relevance. 2014 Philos Ethics Humanit Med
    Vol. 9, pp. 1School: Neuroethics Studies Program, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, 4000 Reservoir Road, Bldg D Rm 238, Washington, DC 20057, USA. jg353@georgetown.edu. 
    DOI URL 
    Abstract: Neuroethics applies cognitive neuroscience for prescribing alterations
    to conceptions of self and society, and for prescriptively judging
    the ethical applications of neurotechnologies. Plentiful normative
    premises are available to ground such prescriptivity, however prescriptive
    neuroethics may remain fragmented by social conventions, cultural
    ideologies, and ethical theories. Herein we offer that an objectively
    principled neuroethics for international relevance requires a new
    meta-ethics: understanding how morality works, and how humans manage
    and improve morality, as objectively based on the brain and social
    sciences. This new meta-ethics will simultaneously equip neuroethics
    for evaluating and revising older cultural ideologies and ethical
    theories, and direct neuroethics towards scientifically valid views
    of encultured humans intelligently managing moralities. Bypassing
    absolutism, cultural essentialisms, and unrealistic ethical philosophies,
    neuroethics arrives at a small set of principles about proper human
    flourishing that are more culturally inclusive and cosmopolitan in
    spirit. This cosmopolitanism in turn suggests augmentations to traditional
    medical ethics in the form of four principled guidelines for international
    consideration: empowerment, non-obsolescence, self-creativity, and
    citizenship.
    BibTeX:
    @article{Shook2014,
      author = {Shook, John R. and Giordano, James},
      title = {A principled and cosmopolitan neuroethics: considerations for international relevance.},
      journal = {Philos Ethics Humanit Med},
      school = {Neuroethics Studies Program, Pellegrino Center for Clinical Bioethics, Georgetown University Medical Center, 4000 Reservoir Road, Bldg D Rm 238, Washington, DC 20057, USA. jg353@georgetown.edu.},
      year = {2014},
      volume = {9},
      pages = {1},
      url = {http://dx.doi.org/10.1186/1747-5341-9-1},
      doi = {http://doi.org/10.1186/1747-5341-9-1}
    }
    
    Smirnov, M.S., Cabral, K.A., Geller, H.M. & Urbach, J.S. The effects of confinement on neuronal growth cone morphology and velocity. 2014 Biomaterials
    Vol. 35(25), pp. 6750-6757School: Department of Physics and the Institute for Soft Matter Synthesis and Metrology, Georgetown University, 320 Regents Hall, Washington, DC 20057, USA. Electronic address: urbach@physics.georgetown.edu. 
    DOI URL 
    Abstract: Optimizing growth cone guidance through the use of patterned substrates
    is important for designing regenerative substrates to aid in recovery
    from neuronal injury. Using laser ablation, we designed micron-scale
    patterns capable of confining dissociated mouse cerebellar granule
    neuron growth cones to channels of different widths ranging from
    1.5 to 12 ?m. Growth cone dynamics in these channels were observed
    using time-lapse microscopy. Growth cone area was decreased in channels
    between 1.5 and 6 ?m as compared to that in 12 ?m and unpatterned
    substrates. Growth cone aspect ratio was also affected as narrower
    channels forced growth cones into a narrow, elongated shape. There
    was no difference in the overall rate of growth cone advance in uniform
    channels between 1.5 and 12 ?m as compared to growth on unpatterned
    substrates. The percentage of time growth cones advanced, paused,
    and retracted was also similar. However, growth cones did respond
    to changes in confinement: growth cones in narrow lanes rapidly sped
    up when encountering a wide region and then slowed down as they entered
    another narrow region. Our results suggest that the rate of neurite
    extension is not affected by the degree of confinement, but does
    respond to changes in confinement.
    BibTeX:
    @article{Smirnov2014,
      author = {Smirnov, Michael S. and Cabral, Katelyn A. and Geller, Herbert M. and Urbach, Jeffrey S.},
      title = {The effects of confinement on neuronal growth cone morphology and velocity.},
      journal = {Biomaterials},
      school = {Department of Physics and the Institute for Soft Matter Synthesis and Metrology, Georgetown University, 320 Regents Hall, Washington, DC 20057, USA. Electronic address: urbach@physics.georgetown.edu.},
      year = {2014},
      volume = {35},
      number = {25},
      pages = {6750--6757},
      url = {http://dx.doi.org/10.1016/j.biomaterials.2014.04.097},
      doi = {http://doi.org/10.1016/j.biomaterials.2014.04.097}
    }
    
    Song, J.M., DiBattista, A.M., Sung, Y.M., Ahn, J.M., Turner, R.S., Yang, J., Pak, D.T.S., Lee, H.-K. & Hoe, H.-S. A tetra(ethylene glycol) derivative of benzothiazole aniline ameliorates dendritic spine density and cognitive function in a mouse model of Alzheimer's disease. 2014 Exp Neurol
    Vol. 252, pp. 105-113School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr. 
    DOI URL 
    Abstract: We recently reported that the tetra(ethylene glycol) derivative of
    benzothiazole aniline, BTA-EG4, acts as an amyloid-binding small
    molecule that promotes dendritic spine density and cognitive function
    in wild-type mice. This raised the possibility that BTA-EG4 may benefit
    the functional decline seen in Alzheimer's disease (AD). In the present
    study, we directly tested whether BTA-EG4 improves dendritic spine
    density and cognitive function in a well-established mouse model
    of AD carrying mutations in APP, PS1 and tau (APPswe;PS1M146V;tauP301L,
    3xTg AD mice). We found that daily injections of BTA-EG4 for 2 weeks
    improved dendritic spine density and cognitive function of 3xTg AD
    mice in an age-dependent manner. Specifically, BTA-EG4 promoted both
    dendritic spine density and morphology alterations in cortical layers
    II/III and in the hippocampus at 6-10 months of age compared to vehicle-injected
    mice. However, at 13-16 months of age, only cortical spine density
    was improved without changes in spine morphology. The changes in
    dendritic spine density correlated with Ras activity, such that 6-10
    month old BTA-EG4 injected 3xTg AD mice had increased Ras activity
    in the cortex and hippocampus, while 13-16 month old mice only trended
    toward an increase in Ras activity in the cortex. Finally, BTA-EG4
    injected 3xTg AD mice at 6-10 months of age showed improved learning
    and memory; however, only minimal improvement was observed at 13-16
    months of age. This behavioral improvement corresponds to a decrease
    in soluble AΒ 40 levels. Taken together, these findings suggest that
    BTA-EG4 may be beneficial in ameliorating the synaptic loss seen
    in early AD.
    BibTeX:
    @article{Song2014,
      author = {Song, Jung Min and DiBattista, Amanda Marie and Sung, You Me and Ahn, Joo Myung and Turner, R Scott and Yang, Jerry and Pak, Daniel T S. and Lee, Hey-Kyoung and Hoe, Hyang-Sook},
      title = {A tetra(ethylene glycol) derivative of benzothiazole aniline ameliorates dendritic spine density and cognitive function in a mouse model of Alzheimer's disease.},
      journal = {Exp Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. Electronic address: sookhoe72@kbri.re.kr.},
      year = {2014},
      volume = {252},
      pages = {105--113},
      url = {http://dx.doi.org/10.1016/j.expneurol.2013.11.023},
      doi = {http://doi.org/10.1016/j.expneurol.2013.11.023}
    }
    
    Stevens, B.W., DiBattista, A.M., William Rebeck, G. & Green, A.E. A gene-brain-cognition pathway for the effect of an Alzheimer?s risk gene on working memory in young adults. 2014 Neuropsychologia
    Vol. 61, pp. 143-149School: Department of Psychology, Georgetown University, 37(th) and O Streets, NW, 302-C White-Gravenor, Washington DC 20057, United States. Electronic address: aeg58@georgetown.edu. 
    DOI URL 
    Abstract: Identifying pathways by which genetic Alzheimer?s disease (AD) risk
    factors exert neurocognitive effects in young adults are essential
    for the effort to develop early interventions to forestall or prevent
    AD onset. Here, in a brain-imaging cohort of 59 young adults, we
    investigated effects of a variant within the clusterin (CLU) gene
    on working memory function and gray matter volume in cortical areas
    that support working memory. In addition, we investigated the extent
    to which effects of CLU genotype on working memory were independent
    of variation in the strongest AD risk factor gene apolipoprotein
    E (APOE). CLU is among the strongest genetic AD risk factors and,
    though it appears to share AD pathogenesis-related features with,
    APOE, it has been far less well studied. CLU genotype was associated
    with working memory performance in our study cohort. Notably, we
    found that variation in gray matter volume in a parietal region,
    previously implicated in maintenance of information for working memory,
    mediated the effect of CLU on working memory performance. APOE genotype
    did not affect working memory within our sample, and did not interact
    with CLU genotype. To our knowledge, this work represents the first
    evidence of a behavioral effect of CLU genotype in young people.
    In addition, this work identifies the first gene-brain-cognition
    mediation effect pathway for the transmission of the effect of an
    AD risk factor. Relative to conventional pairwise associations in
    cognitive neurogenetic research, gene-brain-cognition mediation modeling
    provides a more integrated understanding of how genetic effects transmit
    from gene to brain to cognitive function.
    BibTeX:
    @article{Stevens2014,
      author = {Stevens, Benson W. and DiBattista, Amanda M. and William Rebeck, G. and Green, Adam E.},
      title = {A gene-brain-cognition pathway for the effect of an Alzheimer?s risk gene on working memory in young adults.},
      journal = {Neuropsychologia},
      school = {Department of Psychology, Georgetown University, 37(th) and O Streets, NW, 302-C White-Gravenor, Washington DC 20057, United States. Electronic address: aeg58@georgetown.edu.},
      year = {2014},
      volume = {61},
      pages = {143--149},
      url = {http://dx.doi.org/10.1016/j.neuropsychologia.2014.06.021},
      doi = {http://doi.org/10.1016/j.neuropsychologia.2014.06.021}
    }
    
    Su, X. & Federoff, H.J. Immune responses in Parkinson's disease: interplay between central and peripheral immune systems. 2014 Biomed Res Int
    Vol. 2014, pp. 275178School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA ; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    BibTeX:
    @article{Su2014,
      author = {Su, Xiaomin and Federoff, Howard J.},
      title = {Immune responses in Parkinson's disease: interplay between central and peripheral immune systems.},
      journal = {Biomed Res Int},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA ; Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2014},
      volume = {2014},
      pages = {275178},
      url = {http://dx.doi.org/10.1155/2014/275178},
      doi = {http://doi.org/10.1155/2014/275178}
    }
    
    Tai, A.X. & Kromer, L.F. Corticofugal projections from medial primary somatosensory cortex avoid EphA7-expressing neurons in striatum and thalamus. 2014 Neuroscience
    Vol. 274, pp. 409-418School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA. Electronic address: kromerl@georgetown.edu. 
    DOI URL 
    Abstract: Within the first two postnatal weeks, corticostriatal axons from the
    primary somatosensory cortex (S1) form topographic projections that
    organize into characteristic bands of axon terminals in the dorsolateral
    striatum. Molecules regulating the development of these topographically
    organized projections are currently unknown. Thus, the present study
    investigated whether EphA receptor tyrosine kinases, which regulate
    axonal guidance in the visual system via axon repulsion, could participate
    in the formation of corticostriatal connections during development.
    Prior studies indicate that EphA7-expressing striatal neurons are
    organized into banded compartments resembling the matrisome innervation
    pattern formed by cortical afferents from the S1 cortex and that
    ephrin-A5, a known EphA7 ligand, is expressed in a medial (high)
    to lateral (low) gradient in S1. Thus, we hypothesized that the organization
    of EphA7-expressing striatal neurons in banded domains provides a
    repulsive barrier preventing corticostriatal axons containing EphA7-ligands
    from innervating inappropriate regions of the striatum. To evaluate
    this, we injected the anterograde tracer, biotinylated dextran amine
    (BDA), into two locations in medial areas of S1 (the anterior and
    posterior whisker fields), which are reported to express high levels
    of ephrin-A5 during development. Injections were made in mouse pups
    on postnatal day 9 (P9) and the animals were processed for immunohistochemistry
    on P12. Our data demonstrate that projections from both the forelimb/anterior
    whisker field and the posterior whisker field avoid EphA7-expressing
    neurons and terminate in a banded pattern in regions with very low
    EphA7-expression. We also determined that corticothalamic projections
    from medial S1 also exhibit a restricted distribution in the thalamus
    and avoid neurons expressing EphA7. Thus, our results support the
    hypothesis that the anatomical organization of striatal and thalamic
    neurons expressing EphA7 receptors restricts the topographic distribution
    of cortical afferents from medial regions of S1 which express high
    levels of ephrin-A5.
    BibTeX:
    @article{Tai2014,
      author = {Tai, A. X. and Kromer, L. F.},
      title = {Corticofugal projections from medial primary somatosensory cortex avoid EphA7-expressing neurons in striatum and thalamus.},
      journal = {Neuroscience},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA. Electronic address: kromerl@georgetown.edu.},
      year = {2014},
      volume = {274},
      pages = {409--418},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2014.05.039},
      doi = {http://doi.org/10.1016/j.neuroscience.2014.05.039}
    }
    
    Tamboli, I.Y., Heo, D. & Rebeck, G.W. Extracellular proteolysis of apolipoprotein E (apoE) by secreted serine neuronal protease. 2014 PLoS One
    Vol. 9(3), pp. e93120School: Department of Neuroscience, Georgetown University, Washington DC., United States of America. 
    DOI URL 
    Abstract: Under normal conditions, brain apolipoprotein E (apoE) is secreted
    and lipidated by astrocytes, then taken up by neurons via receptor
    mediated endocytosis. Free apoE is either degraded in intraneuronal
    lysosomal compartments or released. Here we identified a novel way
    by which apoE undergoes proteolysis in the extracellular space via
    a secreted neuronal protease. We show that apoE is cleaved in neuronal
    conditioned media by a secreted serine protease. This apoE cleavage
    was inhibited by PMSF and ?1-antichymotrypsin, but not neuroserpin-1
    or inhibitors of thrombin and cathepsin G, supporting its identity
    as a chymotrypsin like protease. In addition, apoE incubation with
    purified chymotrypsin produced a similar pattern of apoE fragments.
    Analysis of apoE fragments by mass spectrometry showed cleavages
    occurring at the C-terminal side of apoE tryptophan residues, further
    supporting our identification of cleavage by chymotrypsin like protease.
    Hippocampal neurons were more efficient in mediating this apoE cleavage
    than cortical neurons. Proteolysis of apoE4 generated higher levels
    of low molecular weight fragments compared to apoE3. Primary glial
    cultures released an inhibitor of this proteolytic activity. Together,
    these studies reveal novel mechanism by which apoE can be regulated
    and therefore could be useful in designing apoE directed AD therapeutic
    approaches.
    BibTeX:
    @article{Tamboli2014,
      author = {Tamboli, Irfan Y. and Heo, Dongeun and Rebeck, G William},
      title = {Extracellular proteolysis of apolipoprotein E (apoE) by secreted serine neuronal protease.},
      journal = {PLoS One},
      school = {Department of Neuroscience, Georgetown University, Washington DC., United States of America.},
      year = {2014},
      volume = {9},
      number = {3},
      pages = {e93120},
      url = {http://dx.doi.org/10.1371/journal.pone.0093120},
      doi = {http://doi.org/10.1371/journal.pone.0093120}
    }
    
    Trotter, J.H., Lussier, A.L., Psilos, K.E., Mahoney, H.L., Sponaugle, A.E., Hoe, H.-S., Rebeck, G.W. & Weeber, E.J. Extracellular proteolysis of reelin by tissue plasminogen activator following synaptic potentiation. 2014 Neuroscience
    Vol. 274, pp. 299-307School: Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United States; USF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States. Electronic address: eweeber@health.usf.edu. 
    DOI URL 
    Abstract: The secreted glycoprotein reelin plays an indispensable role in neuronal
    migration during development and in regulating adult synaptic functions.
    The upstream mechanisms responsible for initiating and regulating
    the duration and magnitude of reelin signaling are largely unknown.
    Here we report that reelin is cleaved between EGF-like repeats 6-7
    (R6-7) by tissue plasminogen activator (tPA) under cell-free conditions.
    No changes were detected in the level of reelin and its fragments
    in the brains of tPA knockouts, implying that other unknown proteases
    are responsible for generating reelin fragments found constitutively
    in the adult brain. Induction of NMDAR-independent long-term potentiation
    with the potassium channel blocker tetraethylammonium chloride (TEA-Cl)
    led to a specific up-regulation of reelin processing at R6-7 in wild-type
    mice. In contrast, no changes in reelin expression and processing
    were observed in tPA knockouts following TEA-Cl treatment. These
    results demonstrate that synaptic potentiation results in tPA-dependent
    reelin processing and suggest that extracellular proteolysis of reelin
    may regulate reelin signaling in the adult brain.
    BibTeX:
    @article{Trotter2014,
      author = {Trotter, J. H. and Lussier, A. L. and Psilos, K. E. and Mahoney, H. L. and Sponaugle, A. E. and Hoe, H-S. and Rebeck, G. W. and Weeber, E. J.},
      title = {Extracellular proteolysis of reelin by tissue plasminogen activator following synaptic potentiation.},
      journal = {Neuroscience},
      school = {Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United States; USF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States. Electronic address: eweeber@health.usf.edu.},
      year = {2014},
      volume = {274},
      pages = {299--307},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2014.05.046},
      doi = {http://doi.org/10.1016/j.neuroscience.2014.05.046}
    }
    
    Ullrich, L., Dumanis, S.B., Evans, T.M., Jeannotte, A.M., Leonard, C., Rozzi, S.J., Taylor, C.M., Gale, K., Kanwal, J.S., Maguire-Zeiss, K.A., Wolfe, B.B. & Forcelli, P.A. From student to steward: the Interdisciplinary Program in Neuroscience at Georgetown University as a case study in professional development during doctoral training. 2014 Med Educ Online
    Vol. 19, pp. 22623School: Physiology, Georgetown University, Washington, DC, USA; paf22@georgetown.edu. 
     
    Abstract: A key facet of professional development is the formation of professional
    identity. At its most basic level, professional identity for a scientist
    centers on mastery of a discipline and the development of research
    skills during doctoral training. To develop a broader understanding
    of professional identity in the context of doctoral training, the
    Carnegie Initiative on the Doctorate (CID) ran a multi-institutional
    study from 2001 to 2005. A key outcome of the CID was the development
    of the concept of 'stewards of the discipline'. The Interdisciplinary
    Program in Neuroscience (IPN) at Georgetown University participated
    in CID from 2003 to 2005. Here, we describe the IPN and highlight
    the programmatic developments resulting from participation in the
    CID. In particular, we emphasize programmatic activities that are
    designed to promote professional skills in parallel with scientific
    development. We describe activities in the domains of leadership,
    communication, teaching, public outreach, ethics, collaboration,
    and mentorship. Finally, we provide data that demonstrate that traditional
    metrics of academic success are not adversely affected by the inclusion
    of professional development activities in the curricula. By incorporating
    these seven 'professional development' activities into the required
    coursework and dissertation research experience, the IPN motivates
    students to become stewards of the discipline.
    BibTeX:
    @article{Ullrich2014,
      author = {Ullrich, Lauren and Dumanis, Sonya B. and Evans, Tanya M. and Jeannotte, Alexis M. and Leonard, Carrie and Rozzi, Summer J. and Taylor, Caitlin M. and Gale, Karen and Kanwal, Jagmeet S. and Maguire-Zeiss, Kathleen A. and Wolfe, Barry B. and Forcelli, Patrick A.},
      title = {From student to steward: the Interdisciplinary Program in Neuroscience at Georgetown University as a case study in professional development during doctoral training.},
      journal = {Med Educ Online},
      school = { Physiology, Georgetown University, Washington, DC, USA; paf22@georgetown.edu.},
      year = {2014},
      volume = {19},
      pages = {22623}
    }
    
    Washington, P.M., Morffy, N., Parsadanian, M., Zapple, D.N. & Burns, M.P. Experimental traumatic brain injury induces rapid aggregation and oligomerization of amyloid-beta in an Alzheimer's disease mouse model. 2014 J Neurotrauma
    Vol. 31(1), pp. 125-134School: 1 Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center , Washington, DC. 
    DOI URL 
    Abstract: Soluble amyloid-beta (AΒ) oligomers are hypothesized to be the pathogenic
    species in Alzheimer's disease (AD), and increased levels of oligomers
    in the brain subsequent to traumatic brain injury (TBI) may exacerbate
    secondary injury pathways and underlie increased risk of developing
    AD in later life. To determine whether TBI causes AΒ aggregation
    and oligomerization in the brain, we exposed triple transgenic AD
    model mice to controlled cortical impact injury and measured levels
    of soluble, insoluble, and oligomeric AΒ by enzyme-linked immunosorbent
    assay (ELISA) at 1, 3, and 7 days postinjury. TBI rapidly increased
    levels of both soluble and insoluble AΒ40 and AΒ42 in the injured
    cortex at 1 day postinjury. We confirmed previous findings that identified
    damaged axons as a major site of AΒ accumulation using both immunohistochemistry
    and biochemistry. We also report that soluble AΒ oligomers were significantly
    increased in the injured cortex, as demonstrated by both ELISA and
    Western blot. Interestingly, the mouse brain is able to rapidly clear
    trauma-induced AΒ, with both soluble and insoluble AΒ species returning
    to sham levels by 7 days postinjury. In conclusion, we demonstrate
    that TBI causes acute accumulation and aggregation of AΒ in the brain,
    including the formation of low- and high-molecular-weight AΒ oligomers.
    The formation and aggregation of AΒ into toxic species acutely after
    injury may play a role in secondary injury cascades after trauma
    and, chronically, may contribute to increased risk of developing
    AD in later life.
    BibTeX:
    @article{Washington2014,
      author = {Washington, Patricia M. and Morffy, Nicholas and Parsadanian, Maia and Zapple, David N. and Burns, Mark P.},
      title = {Experimental traumatic brain injury induces rapid aggregation and oligomerization of amyloid-beta in an Alzheimer's disease mouse model.},
      journal = {J Neurotrauma},
      school = {1 Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center , Washington, DC.},
      year = {2014},
      volume = {31},
      number = {1},
      pages = {125--134},
      url = {http://dx.doi.org/10.1089/neu.2013.3017},
      doi = {http://doi.org/10.1089/neu.2013.3017}
    }
    
    Wenqiang, C., Lonskaya, I., Hebron, M.L., Ibrahim, Z., Olszewski, R.T., Neale, J.H. & Moussa, C.E.-H. Parkin-mediated reduction of nuclear and soluble TDP-43 reverses behavioral decline in symptomatic mice. 2014 Hum Mol Genet
    Vol. 23(18), pp. 4960-4969School: Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China cem46@georgetown.edu. 
    DOI URL 
    Abstract: The transactivation DNA-binding protein (TDP)-43 binds to thousands
    of mRNAs, but the functional outcomes of this binding remain largely
    unknown. TDP-43 binds to Park2 mRNA, which expresses the E3 ubiquitin
    ligase parkin. We previously demonstrated that parkin ubiquitinates
    TDP-43 and facilitates its translocation from the nucleus to the
    cytoplasm. Here we used brain penetrant tyrosine kinase inhibitors
    (TKIs), including nilotinib and bosutinib and showed that they reduce
    the level of nuclear TDP-43, abrogate its effects on neuronal loss,
    and reverse cognitive and motor decline. Nilotinib decreased soluble
    and insoluble TDP-43, while bosutinib did not affect the insoluble
    level. Parkin knockout mice exhibited high levels of endogenous TDP-43,
    while nilotinib and bosutinib did not alter TDP-43, underscoring
    an indispensable role for parkin in TDP-43 sub-cellular localization.
    These data demonstrate a novel functional relationship between parkin
    and TDP-43 and provide evidence that TKIs are potential therapeutic
    candidates for TDP-43 pathologies.
    BibTeX:
    @article{Wenqiang2014,
      author = {Wenqiang, Chen and Lonskaya, Irina and Hebron, Michaeline L. and Ibrahim, Zainab and Olszewski, Rafal T. and Neale, Joseph H. and Moussa, Charbel E-H.},
      title = {Parkin-mediated reduction of nuclear and soluble TDP-43 reverses behavioral decline in symptomatic mice.},
      journal = {Hum Mol Genet},
      school = {Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China cem46@georgetown.edu.},
      year = {2014},
      volume = {23},
      number = {18},
      pages = {4960--4969},
      url = {http://dx.doi.org/10.1093/hmg/ddu211},
      doi = {http://doi.org/10.1093/hmg/ddu211}
    }
    
    Xu, W., Wolff, B.S. & Wu, J.-y. Low-intensity electric fields induce two distinct response components in neocortical neuronal populations. 2014 J Neurophysiol
    Vol. 112(10), pp. 2446-2456School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia; and wuj@georgetown.edu. 
    DOI URL 
    Abstract: Low-intensity alternating electric fields applied to the scalp are
    capable of modulating cortical activity and brain functions, but
    the underlying mechanisms remain largely unknown. Here, we report
    two distinct components of voltage-sensitive dye signals induced
    by low-intensity, alternating electric fields in rodent cortical
    slices: a "passive component," which corresponds to membrane potential
    changes directly induced by the electric field; and an "active component,"
    which is a widespread depolarization that is dependent on excitatory
    synaptic transmission. The passive component is stationary, with
    amplitude and phase accurately reflecting the cortical cytoarchitecture.
    In contrast, the active component is initiated from a local "hot
    spot" of activity and spreads to a large population as a propagating
    wave with rich local dynamics. The propagation of the active component
    may play a role in modulating large-scale cortical activity by spreading
    a low level of excitation from a small initiation point to a vast
    neuronal population.
    BibTeX:
    @article{Xu2014,
      author = {Xu, Weifeng and Wolff, Brian S. and Wu, Jian-young},
      title = {Low-intensity electric fields induce two distinct response components in neocortical neuronal populations.},
      journal = {J Neurophysiol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia; and wuj@georgetown.edu.},
      year = {2014},
      volume = {112},
      number = {10},
      pages = {2446--2456},
      url = {http://dx.doi.org/10.1152/jn.00740.2013},
      doi = {http://doi.org/10.1152/jn.00740.2013}
    }
    
    Zhao, W., Zhang, J., Davis, E.G. & Rebeck, G.W. Aging reduces glial uptake and promotes extracellular accumulation of AΒ from a lentiviral vector. 2014 Front Aging Neurosci
    Vol. 6, pp. 210School: Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: We used a lentiviral system for expressing secreted human AΒ in the
    brains of young and old APOE knock-in mice. This system allowed us
    to examine AΒ metabolism in vivo, and test the effects of both aging
    and APOE genotype, two of the strongest risk factors for Alzheimer's
    disease. We injected the AΒ1-42 lentivirus into the motor cortex
    of young (2 month old) and old (20-22 month old) APOE3 and APOE4
    mice. After 2 weeks of lentiviral expression, we analyzed the pattern
    of AΒ accumulation, glial activation, and phosphor-tau. In young
    mice, AΒ accumulated mainly within neurons with no evidence of extracellular
    AΒ. Significantly higher levels of intraneuronal AΒ were observed
    in APOE4 mice compared to APOE3 mice. In old mice, APOE4 predisposed
    again to higher levels of AΒ accumulation, but the AΒ was mainly
    in extracellular spaces. In younger mice, we also observed AΒ in
    microglia but not astrocytes. The numbers of microglia containing
    AΒ were significantly higher in APOE3 mice compared to APOE4 mice,
    and were significantly lower in both genetic backgrounds with aging.
    The astrocytes in old mice were activated to a greater extent in
    the brain regions where AΒ was introduced, an effect that was again
    increased by the presence of APOE4. Finally, phospho-tau accumulated
    in the region of AΒ expression, with evidence of extracellular phospho-tau
    increasing with aging. These data suggest that APOE4 predisposes
    to less microglial clearance of AΒ, leading to more intraneuronal
    accumulation. In older brains, decreased clearance leads to more
    extracellular AΒ, and more downstream consequences relating to astrocyte
    activation and phospho-tau accumulation. We conclude that both aging
    and APOE genotype affect pathways related to AΒ metabolism by microglia.
    BibTeX:
    @article{Zhao2014,
      author = {Zhao, Wenjuan and Zhang, Jiguo and Davis, Elizabeth G. and Rebeck, G William},
      title = {Aging reduces glial uptake and promotes extracellular accumulation of AΒ from a lentiviral vector.},
      journal = {Front Aging Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA.},
      year = {2014},
      volume = {6},
      pages = {210},
      url = {http://dx.doi.org/10.3389/fnagi.2014.00210},
      doi = {http://doi.org/10.3389/fnagi.2014.00210}
    }
    
    Anderson, M.A. & Giordano, J. Aequilibrium prudentis: on the necessity for ethics and policy studies in the scientific and technological education of medical professionals. 2013 BMC Med Educ
    Vol. 13, pp. 58School: Department of Microbiology and Immunology, Georgetown University Medical Center, 3900 Reservoir Road, Washington, DC 20057-1440, USA. 
    DOI URL 
    Abstract: The importance of strong science, technology, engineering, and mathematics
    education continues to grow as society, medicine, and the economy
    become increasingly focused and dependent upon bioscientific and
    technological innovation. New advances in frontier sciences (e.g.,
    genetics, neuroscience, bio-engineering, nanoscience, cyberscience)
    generate ethical issues and questions regarding the use of novel
    technologies in medicine and public life.In light of current emphasis
    upon science, technology, engineering, and mathematics education
    (at the pre-collegiate, undergraduate, graduate, and professional
    levels), the pace and extent of advancements in science and biotechnology,
    the increasingly technological orientation and capabilities of medicine,
    and the ways that medicine - as profession and practice - can engage
    such scientific and technological power upon the multi-cultural world-stage
    to affect the human predicament, human condition, and perhaps nature
    of the human being, we argue that it is critical that science, technology,
    engineering, and mathematics education go beyond technical understanding
    and directly address ethical, legal, social, and public policy implications
    of new innovations. Toward this end, we propose a paradigm of integrative
    science, technology, ethics, and policy studies that meets these
    needs through early and continued educational exposure that expands
    extant curricula of science, technology, engineering, and mathematics
    programs from the high school through collegiate, graduate, medical,
    and post-graduate medical education. We posit a synthetic approach
    that elucidates the historical, current, and potential interaction
    of scientific and biotechnological development in addition to the
    ethico-legal and social issues that are important to educate and
    sustain the next generation of medical and biomedical professionals
    who can appreciate, articulate, and address the realities of scientific
    and biotechnological progress given the shifting architectonics of
    the global social milieu.We assert that current trends in science,
    technology, medicine, and global politics dictate that these skills
    will be necessary to responsibly guide ethically sound employment
    of science, technology, and engineering advancements in medicine
    so as to enable more competent and humanitarian practice within an
    increasingly pluralistic world culture.
    BibTeX:
    @article{Anderson2013,
      author = {Anderson, Misti Ault and Giordano, James},
      title = {Aequilibrium prudentis: on the necessity for ethics and policy studies in the scientific and technological education of medical professionals.},
      journal = {BMC Med Educ},
      school = {Department of Microbiology and Immunology, Georgetown University Medical Center, 3900 Reservoir Road, Washington, DC 20057-1440, USA.},
      year = {2013},
      volume = {13},
      pages = {58},
      url = {http://dx.doi.org/10.1186/1472-6920-13-58},
      doi = {http://doi.org/10.1186/1472-6920-13-58}
    }
    
    Avdoshina, V., Bachis, A. & Mocchetti, I. Synaptic dysfunction in human immunodeficiency virus type-1-positive subjects: inflammation or impaired neuronal plasticity? 2013 J Intern Med
    Vol. 273(5), pp. 454-465School: Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: Many people infected with the human immunodeficiency virus type-1
    (HIV) exhibit mild or severe neurological problems, termed HIV-associated
    neurocognitive disorder (HAND), even when receiving antiretroviral
    therapy. Thus, novel adjunctive therapies must be developed to overcome
    the neurotoxic effect of HIV. New therapies require a better understanding
    of the molecular and cellular mechanisms of HIV-induced neurotoxicity
    and the risk factors that, besides inflammation and T-cell depletion
    and drugs of abuse, render the central nervous system (CNS) a target
    of HIV-induced neurotoxicity. HIV appears to impair neuronal plasticity,
    which refers to the innate ability of the CNS respond to injury and
    promote recovery of function. The availability of brain-derived neurotrophic
    factor (BDNF), a potent neurotrophic factor that is present in abundance
    in the adult brain, is essential for neuronal plasticity. BDNF acts
    through a receptor system composed of Trk and p75NTR. Here, we present
    experimental evidence that some of the clinical features of HIV-mediated
    neurological impairment could result from altered BDNF/TrkB/p75NTR
    regulation and function.
    BibTeX:
    @article{Avdoshina2013a,
      author = {Avdoshina, V. and Bachis, A. and Mocchetti, I.},
      title = {Synaptic dysfunction in human immunodeficiency virus type-1-positive subjects: inflammation or impaired neuronal plasticity?},
      journal = {J Intern Med},
      school = {Laboratory of Preclinical Neurobiology, Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2013},
      volume = {273},
      number = {5},
      pages = {454--465},
      url = {http://dx.doi.org/10.1111/joim.12050},
      doi = {http://doi.org/10.1111/joim.12050}
    }
    
    Avdoshina, V., Mocchetti, I., Liu, C., Young, M.A., Anastos, K., Cohen, M., Crystal, H., Pearce, C.L., Golub, E.T. & Tractenberg, R.E. Single-nucleotide polymorphisms in TrkB and risk for depression: findings from the women's interagency HIV study. 2013 J Acquir Immune Defic Syndr
    Vol. 64(2), pp. 138-141School: Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY; §Departments of Medicine, Stroger Hospital and Rush University, Chicago, IL; ?Departments of Neurology and Pathology, SUNY Downstate Medical Center, Brooklyn, NY; ¶Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Departments of **Neurology; ††Biostatistics, Bioinformatics, and Biomathematics; ‡‡Psychiatry, Georgetown University Medical Center, Washington, DC; and §§Collaborative for Research on Outcomes and Metrics, Department of Neurology, Georgetown University Medical Center, Washington, DC. 
    DOI URL 
    Abstract: Individuals infected with HIV type 1 are more likely than noninfected
    individuals to develop depression. HIV lowers brain-derived neurotrophic
    factor (BDNF), a neurotrophic factor whose receptors play a crucial
    role in the pathophysiology of depression. Therefore, we examined
    whether a single-nucleotide polymorphism in the BDNF gene (rs56164415)
    and related receptors TrkB (rs1212171) and p75 (rs2072446) were associated
    with depression in HIV-infected individuals. A total of 1365 HIV-positive
    and 371 HIV-negative female subjects were included. The distribution
    of alleles was analyzed independently in African Americans (non-Hispanic)
    and Caucasians (non-Hispanic). We have found that the absence of
    depressive symptoms in HIV-positive subjects is associated with a
    genetic variation of the TrkB but not with BDNF or p75 genes. This
    mutation explains 0.8% and 4.4% of the variability for the absence
    of depression in African Americans and Caucasians, respectively.
    BibTeX:
    @article{Avdoshina2013,
      author = {Avdoshina, Valeriya and Mocchetti, Italo and Liu, Chenglong and Young, Mary A. and Anastos, Kathryn and Cohen, Mardge and Crystal, Howard and Pearce, Celeste L. and Golub, Elizabeth T. and Tractenberg, Rochelle E.},
      title = {Single-nucleotide polymorphisms in TrkB and risk for depression: findings from the women's interagency HIV study.},
      journal = {J Acquir Immune Defic Syndr},
      school = { Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY; §Departments of Medicine, Stroger Hospital and Rush University, Chicago, IL; ?Departments of Neurology and Pathology, SUNY Downstate Medical Center, Brooklyn, NY; ¶Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Departments of **Neurology; ††Biostatistics, Bioinformatics, and Biomathematics; ‡‡Psychiatry, Georgetown University Medical Center, Washington, DC; and §§Collaborative for Research on Outcomes and Metrics, Department of Neurology, Georgetown University Medical Center, Washington, DC.},
      year = {2013},
      volume = {64},
      number = {2},
      pages = {138--141},
      url = {http://dx.doi.org/10.1097/QAI.0b013e3182a468e9},
      doi = {http://doi.org/10.1097/QAI.0b013e3182a468e9}
    }
    
    Béraud, D., Hathaway, H.A., Trecki, J., Chasovskikh, S., Johnson, D.A., Johnson, J.A., Federoff, H.J., Shimoji, M., Mhyre, T.R. & Maguire-Zeiss, K.A. Microglial Activation and Antioxidant Responses Induced by the Parkinson's Disease Protein α-synuclein. 2013 J Neuroimmune Pharmacol
    Vol. 8(1), pp. 94-117School: Department of Neuroscience, Georgetown University Medical Center, NRB EP08, 3970 Reservoir Road NW, Washington, DC, 20057, USA. 
    DOI URL 
    Abstract: Parkinson's disease (PD) is the second most common age-related neurodegenerative
    disorder typified by tremor, rigidity, akinesia and postural instability
    due in part to the loss of dopamine within the nigrostriatal system.
    The pathologic features of this disorder include the loss of substantia
    nigra dopamine neurons and attendant striatal terminals, the presence
    of large protein-rich neuronal inclusions containing fibrillar α-synuclein
    and increased numbers of activated microglia. Evidence suggests that
    both misfolded α-synuclein and oxidative stress play an important
    role in the pathogenesis of sporadic PD. Here we review evidence
    that α-synuclein activates glia inducing inflammation and that Nrf2-directed
    phase-II antioxidant enzymes play an important role in PD. We also
    provide new evidence that the expression of antioxidant enzymes regulated
    in part by Nrf2 is increased in a mouse model of α-synuclein overexpression.
    We show that misfolded α-synuclein directly activates microglia inducing
    the production and release of the proinflammatory cytokine, TNF-?,
    and increasing antioxidant enzyme expression. Importantly, we demonstrate
    that the precise structure of α-synuclein is important for induction
    of this proinflammatory pathway. This complex α-synuclein-directed
    glial response highlights the importance of protein misfolding, oxidative
    stress and inflammation in PD and represents a potential locus for
    the development of novel therapeutics focused on induction of the
    Nrf2-directed antioxidant pathway and inhibition of protein misfolding.
    BibTeX:
    @article{Beraud2013,
      author = {Béraud, Dawn and Hathaway, Hannah A. and Trecki, Jordan and Chasovskikh, Sergey and Johnson, Delinda A. and Johnson, Jeffrey A. and Federoff, Howard J. and Shimoji, Mika and Mhyre, Timothy R. and Maguire-Zeiss, Kathleen A.},
      title = {Microglial Activation and Antioxidant Responses Induced by the Parkinson's Disease Protein α-synuclein.},
      journal = {J Neuroimmune Pharmacol},
      school = {Department of Neuroscience, Georgetown University Medical Center, NRB EP08, 3970 Reservoir Road NW, Washington, DC, 20057, USA.},
      year = {2013},
      volume = {8},
      number = {1},
      pages = {94--117},
      url = {http://dx.doi.org/10.1007/s11481-012-9401-0},
      doi = {http://doi.org/10.1007/s11481-012-9401-0}
    }
    
    Chevillet, M.A., Jiang, X., Rauschecker, J.P. & Riesenhuber, M. Automatic phoneme category selectivity in the dorsal auditory stream. 2013 J Neurosci
    Vol. 33(12), pp. 5208-5215School: Laboratory for Computational Cognitive Neuroscience, Department of Neuroscience, and Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, Brain-Mind Laboratory, Department of Biomedical Engineering and Computational Science, Aalto University, 02150 Espoo, Finland, and Research and Exploratory Development Department, Johns Hopkins University Applied Physics Laboratory, Laurel, Maryland 20723. 
    DOI URL 
    Abstract: Debates about motor theories of speech perception have recently been
    reignited by a burst of reports implicating premotor cortex (PMC)
    in speech perception. Often, however, these debates conflate perceptual
    and decision processes. Evidence that PMC activity correlates with
    task difficulty and subject performance suggests that PMC might be
    recruited, in certain cases, to facilitate category judgments about
    speech sounds (rather than speech perception, which involves decoding
    of sounds). However, it remains unclear whether PMC does, indeed,
    exhibit neural selectivity that is relevant for speech decisions.
    Further, it is unknown whether PMC activity in such cases reflects
    input via the dorsal or ventral auditory pathway, and whether PMC
    processing of speech is automatic or task-dependent. In a novel modified
    categorization paradigm, we presented human subjects with paired
    speech sounds from a phonetic continuum but diverted their attention
    from phoneme category using a challenging dichotic listening task.
    Using fMRI rapid adaptation to probe neural selectivity, we observed
    acoustic-phonetic selectivity in left anterior and left posterior
    auditory cortical regions. Conversely, we observed phoneme-category
    selectivity in left PMC that correlated with explicit phoneme-categorization
    performance measured after scanning, suggesting that PMC recruitment
    can account for performance on phoneme-categorization tasks. Structural
    equation modeling revealed connectivity from posterior, but not anterior,
    auditory cortex to PMC, suggesting a dorsal route for auditory input
    to PMC. Our results provide evidence for an account of speech processing
    in which the dorsal stream mediates automatic sensorimotor integration
    of speech and may be recruited to support speech decision tasks.
    BibTeX:
    @article{Chevillet2013,
      author = {Chevillet, Mark A. and Jiang, Xiong and Rauschecker, Josef P. and Riesenhuber, Maximilian},
      title = {Automatic phoneme category selectivity in the dorsal auditory stream.},
      journal = {J Neurosci},
      school = {Laboratory for Computational Cognitive Neuroscience, Department of Neuroscience, and Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, Brain-Mind Laboratory, Department of Biomedical Engineering and Computational Science, Aalto University, 02150 Espoo, Finland, and Research and Exploratory Development Department, Johns Hopkins University Applied Physics Laboratory, Laurel, Maryland 20723.},
      year = {2013},
      volume = {33},
      number = {12},
      pages = {5208--5215},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.1870-12.2013},
      doi = {http://doi.org/10.1523/JNEUROSCI.1870-12.2013}
    }
    
    Dumanis, S.B., DiBattista, A.M., Miessau, M., Moussa, C.E.H. & Rebeck, G.W. APOE genotype affects the pre-synaptic compartment of glutamatergic nerve terminals. 2013 J Neurochem
    Vol. 124(1), pp. 4-14School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Apolipoprotein E (APOE) genotype affects outcomes of Alzheimer's disease
    and other conditions of brain damage. Using APOE knock-in mice, we
    have previously shown that APOE-?4 Targeted Replacement (TR) mice
    have fewer dendritic spines and reduced branching in cortical neurons.
    As dendritic spines are post-synaptic sites of excitatory neurotransmission,
    we used APOE TR mice to examine whether APOE genotype affected the
    various elements of the glutamate-glutamine cycle. We found that
    levels of glutamine synthetase and glutamate uptake transporters
    were unchanged among the APOE genotypes. However, compared with APOE-?3
    TR mice, APOE-?4 TR mice had decreased glutaminase levels (18
    p < 0.05), suggesting decreased conversion of glutamine to glutamate.
    APOE-?4 TR mice also had increased levels of the vesicular glutamate
    transporter 1 (20 p < 0.05), suggesting that APOE genotype affects
    pre-synaptic terminal composition. To address whether these changes
    affected normal neurotransmission, we examined the production and
    metabolism of glutamate and glutamine at 4-5 months and 1 year. Using
    high-frequency (13)C/(1)H nuclear magnetic resonance spectroscopy,
    we found that APOE-?4 TR mice have decreased production of glutamate
    and increased levels of glutamine. These factors may contribute to
    the increased risk of neurodegeneration associated with APOE-?4,
    and also act as surrogate markers for Alzheimer's disease risk.
    BibTeX:
    @article{Dumanis2013,
      author = {Dumanis, Sonya B. and DiBattista, Amanda M. and Miessau, Matthew and Moussa, Charbel E H. and Rebeck, G William},
      title = {APOE genotype affects the pre-synaptic compartment of glutamatergic nerve terminals.},
      journal = {J Neurochem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {124},
      number = {1},
      pages = {4--14},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2012.07908.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2012.07908.x}
    }
    
    Dumanis, S.B., Ullrich, L., Washington, P.M. & Forcelli, P.A. It's money! Real-world grant experience through a student-run, peer-reviewed program. 2013 CBE Life Sci Educ
    Vol. 12(3), pp. 419-428School: Interdisciplinary Program in Neuroscience, School of Medicine, Georgetown University, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Grantsmanship is an integral component of surviving and thriving in
    academic science, especially in the current funding climate. Therefore,
    any additional opportunities to write, read, and review grants during
    graduate school may have lasting benefits on one's career. We present
    here our experience with a small, student-run grant program at Georgetown
    University Medical Center. Founded in 2010, this program has several
    goals: 1) to give graduate students an opportunity to conduct small,
    independent research projects; 2) to encourage graduate students
    to write grants early and often; and 3) to give graduate students
    an opportunity to review grants. In the 3 yr since the program's
    start, 28 applications have been submitted, 13 of which were funded
    for a total of $40,000. From funded grants, students have produced
    abstracts and manuscripts, generated data to support subsequent grant
    proposals, and made new professional contacts with collaborators.
    Above and beyond financial support, this program provided both applicants
    and reviewers an opportunity to improve their writing skills, professional
    development, and understanding of the grants process, as reflected
    in the outcome measures presented. With a small commitment of time
    and funding, other institutions could implement a program like this
    to the benefit of their graduate students.
    BibTeX:
    @article{Dumanis2013a,
      author = {Dumanis, Sonya B. and Ullrich, Lauren and Washington, Patricia M. and Forcelli, Patrick A.},
      title = {It's money! Real-world grant experience through a student-run, peer-reviewed program.},
      journal = {CBE Life Sci Educ},
      school = {Interdisciplinary Program in Neuroscience, School of Medicine, Georgetown University, Washington, DC 20007, USA.},
      year = {2013},
      volume = {12},
      number = {3},
      pages = {419--428},
      url = {http://dx.doi.org/10.1187/cbe.12-05-0058},
      doi = {http://doi.org/10.1187/cbe.12-05-0058}
    }
    
    Dye, C.D., Walenski, M., Prado, E.L., Mostofsky, S. & Ullman, M.T. Children's computation of complex linguistic forms: a study of frequency and imageability effects. 2013 PLoS One
    Vol. 8(9), pp. e74683School: Centre for Research in Linguistics and Language Sciences, Newcastle University, Newcastle Upon Tyne, Tyne and Wear, United Kingdom ; Brain and Language Lab, Department of Neuroscience, Georgetown University, Washington, DC, United States of America. 
    DOI URL 
    Abstract: This study investigates the storage vs. composition of inflected forms
    in typically-developing children. Children aged 8-12 were tested
    on the production of regular and irregular past-tense forms. Storage
    (vs. composition) was examined by probing for past-tense frequency
    effects and imageability effects--both of which are diagnostic tests
    for storage--while controlling for a number of confounding factors.
    We also examined sex as a factor. Irregular inflected forms, which
    must depend on stored representations, always showed evidence of
    storage (frequency and/or imageability effects), not only across
    all children, but also separately in both sexes. In contrast, for
    regular forms, which could be either stored or composed, only girls
    showed evidence of storage. This pattern is similar to that found
    in previously-acquired adult data from the same task, with the notable
    exception that development affects which factors influence the storage
    of regulars in females: imageability plays a larger role in girls,
    and frequency in women. Overall, the results suggest that irregular
    inflected forms are always stored (in children and adults, and in
    both sexes), whereas regulars can be either composed or stored, with
    their storage a function of various item- and subject-level factors.
    BibTeX:
    @article{Dye2013,
      author = {Dye, Cristina D. and Walenski, Matthew and Prado, Elizabeth L. and Mostofsky, Stewart and Ullman, Michael T.},
      title = {Children's computation of complex linguistic forms: a study of frequency and imageability effects.},
      journal = {PLoS One},
      school = {Centre for Research in Linguistics and Language Sciences, Newcastle University, Newcastle Upon Tyne, Tyne and Wear, United Kingdom ; Brain and Language Lab, Department of Neuroscience, Georgetown University, Washington, DC, United States of America.},
      year = {2013},
      volume = {8},
      number = {9},
      pages = {e74683},
      url = {http://dx.doi.org/10.1371/journal.pone.0074683},
      doi = {http://doi.org/10.1371/journal.pone.0074683}
    }
    
    Evans, T.M., Flowers, D.L., Napoliello, E.M. & Eden, G.F. Sex-specific gray matter volume differences in females with developmental dyslexia. 2013 Brain Struct FunctSchool: Center for the Study of Learning, Department of Pediatrics, Georgetown University Medical Center, BOX 571406, Suite 150, Building D, 4000 Reservoir Road, NW, Washington, DC, 20057, USA.  DOI URL 
    Abstract: Developmental dyslexia, characterized by unexpected reading difficulty,
    is associated with anomalous brain anatomy and function. Previous
    structural neuroimaging studies have converged in reports of less
    gray matter volume (GMV) in dyslexics within left hemisphere regions
    known to subserve language. Due to the higher prevalence of dyslexia
    in males, these studies are heavily weighted towards males, raising
    the question whether studies of dyslexia in females only and using
    the same techniques, would generate the same findings. In a replication
    study of men, we obtained the same findings of less GMV in dyslexics
    in left middle/inferior temporal gyri and right postcentral/supramarginal
    gyri as reported in the literature. However, comparisons in women
    with and without dyslexia did not yield left hemisphere differences,
    and instead, we found less GMV in right precuneus and paracentral
    lobule/medial frontal gyrus. In boys, we found less GMV in left inferior
    parietal cortex (supramarginal/angular gyri), again consistent with
    previous work, while in girls differences were within right central
    sulcus, spanning adjacent gyri, and left primary visual cortex. Our
    investigation into anatomical variants in dyslexia replicates existing
    studies in males, but at the same time shows that dyslexia in females
    is not characterized by involvement of left hemisphere language regions
    but rather early sensory and motor cortices (i.e., motor and premotor
    cortex, primary visual cortex). Our findings suggest that models
    on the brain basis of dyslexia, primarily developed through the study
    of males, may not be appropriate for females and suggest a need for
    more sex-specific investigations into dyslexia.
    BibTeX:
    @article{Evans2013,
      author = {Evans, Tanya M. and Flowers, D Lynn and Napoliello, Eileen M. and Eden, Guinevere F.},
      title = {Sex-specific gray matter volume differences in females with developmental dyslexia.},
      journal = {Brain Struct Funct},
      school = {Center for the Study of Learning, Department of Pediatrics, Georgetown University Medical Center, BOX 571406, Suite 150, Building D, 4000 Reservoir Road, NW, Washington, DC, 20057, USA.},
      year = {2013},
      url = {http://dx.doi.org/10.1007/s00429-013-0552-4},
      doi = {http://doi.org/10.1007/s00429-013-0552-4}
    }
    
    Fiandaca, M.S. & Federoff, H.J. Using viral-mediated gene delivery to model Parkinson's disease: Do nonhuman primate investigations expand our understanding? 2013 Exp NeurolSchool: Department of Neurology, Georgetown University, Washington, D.C. 20007; Department of Neuroscience, Georgetown University, Washington, D.C. 20007.  DOI URL 
    Abstract: In this review, we consider the use of nonhuman primate (NHP) models
    of Parkinson's disease (PD) produced using viral-mediated gene delivery
    and information they provide in comparison to other model systems
    in rodents and NHPs. To date, rodent and NHP PD models have found
    it difficult to fully recapitulate the human disorder and, therefore,
    provide little actual insight into disease progression. The viral-mediated
    gene delivery method for α-synuclein has been shown to produce a
    parkinsonian rodent and NHP. This novel viral-mediated gene transfer
    model in the NHP appears to provide a significant advance beyond
    neurotoxicant models, by more closely mimicking the more chronic
    time course of developed behavioral deterioration and neuropathology.
    Although we agree that the use of these novel methods inducing parkinsonian
    NHPs may provide relevant treatment insights, beyond those of more
    standard PD models, we remain cautious as to the preclinical models'
    ability to predict outcomes in human trials. In specific cases of
    certain novel medical therapeutics, therefore, we also consider the
    phase 0 clinical trial as offering an alternative to the currently
    non-predictive preclinical models, including those in the NHP.
    BibTeX:
    @article{Fiandaca2013,
      author = {Fiandaca, Massimo S. and Federoff, Howard J.},
      title = {Using viral-mediated gene delivery to model Parkinson's disease: Do nonhuman primate investigations expand our understanding?},
      journal = {Exp Neurol},
      school = {Department of Neurology, Georgetown University, Washington, D.C. 20007; Department of Neuroscience, Georgetown University, Washington, D.C. 20007.},
      year = {2013},
      url = {http://dx.doi.org/10.1016/j.expneurol.2013.03.014},
      doi = {http://doi.org/10.1016/j.expneurol.2013.03.014}
    }
    
    Glezer, L.S. & Riesenhuber, M. Individual variability in location impacts orthographic selectivity in the "visual word form area". 2013 J Neurosci
    Vol. 33(27), pp. 11221-11226School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20007, USA. lsg5@georgetown.edu 
    DOI URL 
    Abstract: Strong evidence exists for a key role of the human ventral occipitotemporal
    cortex (vOT) in reading, yet there have been conflicting reports
    about the specificity of this area in orthographic versus nonorthographic
    processing. We suggest that the inconsistencies in the literature
    can be explained by the method used to identify regions that respond
    to words. Here we provide evidence that the "visual word form area"
    (VWFA) shows word selectivity when identified at the individual subject
    level, but that intersubject variability in the location and size
    of the VWFA causes this selectivity to be washed out if defining
    the VWFA at the group level or based on coordinates from the literature.
    Our findings confirm the existence of a word-selective region in
    vOT while providing an explanation for why other studies have found
    a lack of word specificity in vOT.
    BibTeX:
    @article{Glezer2013,
      author = {Glezer, Laurie S. and Riesenhuber, Maximilian},
      title = {Individual variability in location impacts orthographic selectivity in the "visual word form area".},
      journal = {J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20007, USA. lsg5@georgetown.edu},
      year = {2013},
      volume = {33},
      number = {27},
      pages = {11221--11226},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.5002-12.2013},
      doi = {http://doi.org/10.1523/JNEUROSCI.5002-12.2013}
    }
    
    Gordon, E.M., Devaney, J.M., Bean, S. & Vaidya, C.J. Resting-State Striato-Frontal Functional Connectivity is Sensitive to DAT1 Genotype and Predicts Executive Function. 2013 Cereb CortexSchool: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.  DOI URL 
    Abstract: Individual differences in striatal dopamine (DA) signaling have been
    associated both with individual differences in executive function
    in healthy individuals and with risk for psychiatric disorders defined
    by executive dysfunction. We used resting-state functional connectivity
    in 50 healthy adults to examine whether a polymorphism of the dopamine
    transporter gene (DAT1), which regulates striatal DA function, affects
    striatal functional connectivity in healthy adults, and whether that
    connectivity predicts executive function. We found that 9/10 heterozygotes,
    who are believed to have higher striatal DA signaling, demonstrated
    stronger connectivity between dorsal caudate (DC) and insular, dorsal
    anterior cingulate, and dorsolateral prefrontal regions, as well
    as between ventral striatum and ventrolateral prefrontal cortex,
    than 10/10 homozygotes. Across subjects, stronger DC-seeded connectivity
    predicted superior N-back working memory performance, while stronger
    ventral striatum-seeded connectivity predicted reduced impulsivity
    in everyday life. Further, mediation analysis suggested that connectivity
    strength mediated relationships between DAT1 genotype and behavior.
    These findings suggest that resting-state striato-frontal connectivity
    may be an endophenotype for executive function in healthy individuals.
    BibTeX:
    @article{Gordon2013,
      author = {Gordon, Evan M. and Devaney, Joseph M. and Bean, Stephanie and Vaidya, Chandan J.},
      title = {Resting-State Striato-Frontal Functional Connectivity is Sensitive to DAT1 Genotype and Predicts Executive Function.},
      journal = {Cereb Cortex},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2013},
      url = {http://dx.doi.org/10.1093/cercor/bht229},
      doi = {http://doi.org/10.1093/cercor/bht229}
    }
    
    Hebron, M.L., Algarzae, N.K., Lonskaya, I. & Moussa, C. Fractalkine signaling and Tau hyper-phosphorylation are associated with autophagic alterations in lentiviral Tau and AΒ(1-42) gene transfer models. 2013 Exp NeurolSchool: Department of Neuroscience, Georgetown University Medical Center, Washington D.C. 20007, USA; Department of Biochemistry and Cell Biology, Georgetown University Medical Center, Washington D.C. 20007, USA.  DOI URL 
    Abstract: Tau hyper-phosphorylation (p-Tau) and neuro-inflammation are hallmarks
    of neurodegeneration. Previous findings suggest that microglial activation
    via CX3CL1 promotes p-Tau. We examined inflammation and autophagic
    p-Tau clearance in lentiviral Tau and mutant P301L expressing rats
    and used lentiviral AΒ(1-42) to induce p-Tau. Lentiviral Tau or P301L
    expression significantly increased caspase-3 activity and TNF-?,
    but CX3CL1 was significantly higher in animals expressing Tau compared
    to P301L. Lentiviral AΒ(1-42) induced p-Tau 4weeks post-injection,
    and increased caspase-3 activation (8-fold) and TNF-? levels. Increased
    levels of ADAM-10/17 were also detected with p-Tau. IL-6 levels were
    increased but CX3CL1 did not change in the absence of p-Tau (2weeks);
    however, p-Tau reversed these effects, which were associated with
    increased microglial activity. We observed changes in autophagic
    markers, including accumulation of autophagic vacuoles (AVs) and
    p-Tau accumulation in autophagosomes but not lysosomes, suggesting
    alteration of autophagy. Taken together, microglial activation may
    promote p-Tau independent of total Tau levels via CX3CL1 signaling,
    which seems to depend on interaction with inflammatory markers, mainly
    IL-6. The simultaneous change in autophagy and CX3CL1 signaling suggests
    communication between microglia and neurons, raising the possibility
    that accumulation of intraneuronal amyloid, due to lack of autophagic
    clearance, may lead microglia activation to promote p-Tau as a tag
    for phagocytic degradation.
    BibTeX:
    @article{Hebron2013,
      author = {Hebron, Michaeline L. and Algarzae, Norah K. and Lonskaya, Irina and Moussa, Charbel},
      title = {Fractalkine signaling and Tau hyper-phosphorylation are associated with autophagic alterations in lentiviral Tau and AΒ(1-42) gene transfer models.},
      journal = {Exp Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington D.C. 20007, USA; Department of Biochemistry and Cell Biology, Georgetown University Medical Center, Washington D.C. 20007, USA.},
      year = {2013},
      url = {http://dx.doi.org/10.1016/j.expneurol.2013.01.009},
      doi = {http://doi.org/10.1016/j.expneurol.2013.01.009}
    }
    
    Hebron, M.L., Lonskaya, I. & Moussa, C.E.-H. Tyrosine kinase inhibition facilitates autophagic SNCA/α-synuclein clearance. 2013 Autophagy
    Vol. 9(8), pp. 1249-1250School: Department of Neuroscience; Laboratory for Dementia and Parkinsonism; Georgetown University Medical Center; Washington DC, USA. 
    DOI URL 
    Abstract: The effects of ABL1/ABL inhibition on clearance of SNCA/α-synuclein
    were evaluated in animal models of α-synucleinopathies. Parkinson
    disease (PD) is a movement disorder characterized by death of dopaminergic
    substantia nigra (SN) neurons and brain accumulation of SNCA. The
    tyrosine kinase ABL1 is activated in several neurodegenerative diseases.
    An increase in ABL1 activity is detected in human postmortem PD brains.
    Lentiviral expression of SNCA in the mouse SN activates ABL1 via
    phosphorylation, while lentiviral Abl expression increases SNCA levels.
    Administration of the brain-penetrant tyrosine kinase inhibitor Nilotinib
    decreases Abl activity and facilitates autophagic clearance of SNCA
    in transgenic and lentiviral gene transfer models. Subcellular fractionation
    demonstrates accumulation of SNCA and hyperphosphorylated MAPT/Tau
    (p-MAPT) in autophagic vacuoles in SNCA-expressing brains, while
    Nilotinib treatment leads to protein deposition into the lysosomes,
    suggesting enhanced autophagic clearance. These data suggest that
    Nilotinib may be a therapeutic strategy to degrade SNCA in PD and
    other α-synucleinopathies.
    BibTeX:
    @article{Hebron2013b,
      author = {Hebron, Michaeline L. and Lonskaya, Irina and Moussa, Charbel E-H.},
      title = {Tyrosine kinase inhibition facilitates autophagic SNCA/α-synuclein clearance.},
      journal = {Autophagy},
      school = {Department of Neuroscience; Laboratory for Dementia and Parkinsonism; Georgetown University Medical Center; Washington DC, USA.},
      year = {2013},
      volume = {9},
      number = {8},
      pages = {1249--1250},
      url = {http://dx.doi.org/10.4161/auto.25368},
      doi = {http://doi.org/10.4161/auto.25368}
    }
    
    Hebron, M.L., Lonskaya, I. & Moussa, C.E.-H. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson's disease models. 2013 Hum Mol Genet
    Vol. 22(16), pp. 3315-3328School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Parkinson's disease is a movement disorder characterized by death
    of dopaminergic substantia nigra (SN) neurons and brain accumulation
    of α-synuclein. The tyrosine kinase Abl is activated in neurodegeneration.
    Here, we show that lentiviral expression of α-synuclein in the mouse
    SN leads to Abl activation (phosphorylation) and lentiviral Abl expression
    increases α-synuclein levels, in agreement with Abl activation in
    PD brains. Administration of the tyrosine kinase inhibitor nilotinib
    decreases Abl activity and ameliorates autophagic clearance of α-synuclein
    in transgenic and lentiviral gene transfer models. Subcellular fractionation
    shows accumulation of α-synuclein and hyper-phosphorylated Tau (p-Tau)
    in autophagic vacuoles in α-synuclein expressing brains, but nilotinib
    enhances protein deposition into the lysosomes. Nilotinib is used
    for adult leukemia treatment and it enters the brain within US Food
    and Drug Administration approved doses, leading to autophagic degradation
    of α-synuclein, protection of SN neurons and amelioration of motor
    performance. These data suggest that nilotinib may be a therapeutic
    strategy to degrade α-synuclein in PD and other α-synucleinopathies.
    BibTeX:
    @article{Hebron2013c,
      author = {Hebron, Michaeline L. and Lonskaya, Irina and Moussa, Charbel E-H.},
      title = {Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of α-synuclein in Parkinson's disease models.},
      journal = {Hum Mol Genet},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {22},
      number = {16},
      pages = {3315--3328},
      url = {http://dx.doi.org/10.1093/hmg/ddt192},
      doi = {http://doi.org/10.1093/hmg/ddt192}
    }
    
    Hebron, M.L., Lonskaya, I., Sharpe, K., Weerasinghe, P.P.K., Algarzae, N.K., Shekoyan, A.R. & Moussa, C.E.-H. Parkin ubiquitinates Tar-DNA binding protein-43 (TDP-43) and promotes its cytosolic accumulation via interaction with histone deacetylase 6 (HDAC6). 2013 J Biol Chem
    Vol. 288(6), pp. 4103-4115School: Department of Neuroscience, Georgetown University Medical Center, Washington, D. C. 20007, USA. 
    DOI URL 
    Abstract: The importance of E3 ubiquitin ligases, involved in the degradation
    of misfolded proteins or promotion of protein-protein interaction,
    is increasingly recognized in neurodegeneration. TDP-43 is a predominantly
    nuclear protein, which regulates the transcription of thousands of
    genes and binds to mRNA of the E3 ubiquitin ligase Parkin to regulate
    its expression. Wild type and mutated TDP-43 are detected in ubiquitinated
    forms within the cytosol in several neurodegenerative diseases. We
    elucidated the mechanisms of TDP-43 interaction with Parkin using
    transgenic A315T mutant TDP-43 (TDP43-Tg) mice, lentiviral wild type
    TDP-43, and Parkin gene transfer rat models. TDP-43 expression increased
    Parkin mRNA and protein levels. Lentiviral TDP-43 increased the levels
    of nuclear and cytosolic protein, whereas Parkin co-expression mediated
    Lys-48 and Lys-63-linked ubiquitin to TDP-43 and led to cytosolic
    co-localization of Parkin with ubiquitinated TDP-43. Parkin and TDP-43
    formed a multiprotein complex with HDAC6, perhaps to mediate TDP-43
    translocation. In conclusion, Parkin ubiquitinates TDP-43 and facilitates
    its cytosolic accumulation through a multiprotein complex with HDAC6.
    BibTeX:
    @article{Hebron2013a,
      author = {Hebron, Michaeline L. and Lonskaya, Irina and Sharpe, Kaydee and Weerasinghe, Puwakdandawe P K. and Algarzae, Norah K. and Shekoyan, Ashot R. and Moussa, Charbel E-H.},
      title = {Parkin ubiquitinates Tar-DNA binding protein-43 (TDP-43) and promotes its cytosolic accumulation via interaction with histone deacetylase 6 (HDAC6).},
      journal = {J Biol Chem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, D. C. 20007, USA.},
      year = {2013},
      volume = {288},
      number = {6},
      pages = {4103--4115},
      url = {http://dx.doi.org/10.1074/jbc.M112.419945},
      doi = {http://doi.org/10.1074/jbc.M112.419945}
    }
    
    Howard, Jr, J.H. & Howard, D.V. Aging mind and brain: is implicit learning spared in healthy aging? 2013 Front Psychol
    Vol. 4, pp. 817School: Department of Psychology, The Catholic University of America Washington, DC, USA ; Department of Psychology, Georgetown University Washington, DC, USA. 
    DOI URL 
    Abstract: It is often held that although explicit learning declines in the course
    of normal aging, implicit learning is relatively preserved. Here
    we summarize research from our group which leads us to argue that
    some forms of implicit learning do decline with adult age. In particular,
    we propose that there are age-related declines in implicit learning
    of probabilistic sequential relationships that occur across the adult
    lifespan, and that they reflect, at least in part, age-related striatal
    dysfunction. We first review behavioral evidence supporting this
    age-related decline and then evidence from patient groups, genetics,
    and neuroimaging supporting this striatal dysfunction hypothesis.
    BibTeX:
    @article{Howard2013,
      author = {Howard, Jr, James H and Howard, Darlene V.},
      title = {Aging mind and brain: is implicit learning spared in healthy aging?},
      journal = {Front Psychol},
      school = {Department of Psychology, The Catholic University of America Washington, DC, USA ; Department of Psychology, Georgetown University Washington, DC, USA.},
      year = {2013},
      volume = {4},
      pages = {817},
      url = {http://dx.doi.org/10.3389/fpsyg.2013.00817},
      doi = {http://doi.org/10.3389/fpsyg.2013.00817}
    }
    
    Huang, L., Shimoji, M., Wang, J., Shah, S., Kamila, S., Biehl, E.R., Lim, S., Chang, A., Maguire-Zeiss, K.A., Su, X. & Federoff, H.J. Development of inducible leucine-rich repeat kinase 2 (LRRK2) cell lines for therapeutics development in Parkinson's disease. 2013 Neurotherapeutics
    Vol. 10(4), pp. 840-851School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: The pathogenic mechanism(s) contributing to loss of dopamine neurons
    in Parkinson's disease (PD) remain obscure. Leucine-rich repeat kinase
    2 (LRRK2) mutations are linked, as a causative gene, to PD. LRRK2
    mutations are estimated to account for 10% of familial and between
    1 % and 3 % of sporadic PD. LRRK2 proximate single nucleotide polymorphisms
    have also been significantly associated with idiopathic/sporadic
    PD by genome-wide association studies. LRRK2 is a multidomain-containing
    protein and belongs to the protein kinase super-family. We constructed
    two inducible dopaminergic cell lines expressing either human-LRRK2-wild-type
    or human-LRRK2-mutant (G2019S). Phenotypes of these LRRK2 cell lines
    were examined with respect to cell viability, morphology, and protein
    function with or without induction of LRRK2 gene expression. The
    overexpression of G2019S gene promoted (1) low cellular metabolic
    activity without affecting cell viability, (2) blunted neurite extension,
    and (3) increased phosphorylation at S910 and S935. Our observations
    are consistent with reported general phenotypes in LRRK2 cell lines
    by other investigators. We used these cell lines to interrogate the
    biological function of LRRK2, to evaluate their potential as a drug-screening
    tool, and to investigate screening for small hairpin RNA-mediated
    LRRK2 G2019S gene knockdown as a potential therapeutic strategy.
    A proposed LRRK2 kinase inhibitor (i.e., IN-1) decreased LRRK2 S910
    and S935 phosphorylation in our MN9DLRRK2 cell lines in a dose-dependent
    manner. Lentivirus-mediated transfer of LRRK2 G2019S allele-specific
    small hairpin RNA reversed the blunting of neurite extension caused
    by LRRK2 G2019S overexpression. Taken together, these inducible LRRK2
    cell lines are suitable reagents for LRRK2 functional studies, and
    the screening of potential LRRK2 therapeutics.
    BibTeX:
    @article{Huang2013a,
      author = {Huang, Liang and Shimoji, Mika and Wang, Juan and Shah, Salim and Kamila, Sukanta and Biehl, Edward R. and Lim, Seung and Chang, Allison and Maguire-Zeiss, Kathleen A. and Su, Xiaomin and Federoff, Howard J.},
      title = {Development of inducible leucine-rich repeat kinase 2 (LRRK2) cell lines for therapeutics development in Parkinson's disease.},
      journal = {Neurotherapeutics},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2013},
      volume = {10},
      number = {4},
      pages = {840--851},
      url = {http://dx.doi.org/10.1007/s13311-013-0208-3},
      doi = {http://doi.org/10.1007/s13311-013-0208-3}
    }
    
    Huang, L., Su, X. & Federoff, H.J. Single-chain fragment variable passive immunotherapies for neurodegenerative diseases. 2013 Int J Mol Sci
    Vol. 14(9), pp. 19109-19127School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. hjf8@georgetown.edu. 
    DOI URL 
    Abstract: Accumulation of misfolded proteins has been implicated in a variety
    of neurodegenerative diseases including prion diseases, Alzheimer's
    disease (AD), Parkinson's disease (PD), and Huntington's disease
    (HD). In the past decade, single-chain fragment variable (scFv) -based
    immunotherapies have been developed to target abnormal proteins or
    various forms of protein aggregates including AΒ, SNCA, Htt, and
    PrP proteins. The scFvs are produced by fusing the variable regions
    of the antibody heavy and light chains, creating a much smaller protein
    with unaltered specificity. Because of its small size and relative
    ease of production, scFvs are promising diagnostic and therapeutic
    reagents for protein misfolded diseases. Studies have demonstrated
    the efficacy and safety of scFvs in preventing amyloid protein aggregation
    in preclinical models. Herein, we discuss recent developments of
    these immunotherapeutics. We review efforts of our group and others
    using scFv in neurodegenerative disease models. We illustrate the
    advantages of scFvs, including engineering to enhance misfolded conformer
    specificity and subcellular targeting to optimize therapeutic action.
    BibTeX:
    @article{Huang2013,
      author = {Huang, Liang and Su, Xiaomin and Federoff, Howard J.},
      title = {Single-chain fragment variable passive immunotherapies for neurodegenerative diseases.},
      journal = {Int J Mol Sci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. hjf8@georgetown.edu.},
      year = {2013},
      volume = {14},
      number = {9},
      pages = {19109--19127},
      url = {http://dx.doi.org/10.3390/ijms140919109},
      doi = {http://doi.org/10.3390/ijms140919109}
    }
    
    Jiang, X., Bollich, A., Cox, P., Hyder, E., James, J., Gowani, S.A., Hadjikhani, N., Blanz, V., Manoach, D.S., Barton, J.J.S., Gaillard, W.D. & Riesenhuber, M. A quantitative link between face discrimination deficits and neuronal selectivity for faces in autism. 2013 Neuroimage Clin
    Vol. 2, pp. 320-331School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Individuals with Autism Spectrum Disorder (ASD) appear to show a general
    face discrimination deficit across a range of tasks including social-emotional
    judgments as well as identification and discrimination. However,
    functional magnetic resonance imaging (fMRI) studies probing the
    neural bases of these behavioral differences have produced conflicting
    results: while some studies have reported reduced or no activity
    to faces in ASD in the Fusiform Face Area (FFA), a key region in
    human face processing, others have suggested more typical activation
    levels, possibly reflecting limitations of conventional fMRI techniques
    to characterize neuron-level processing. Here, we test the hypotheses
    that face discrimination abilities are highly heterogeneous in ASD
    and are mediated by FFA neurons, with differences in face discrimination
    abilities being quantitatively linked to variations in the estimated
    selectivity of face neurons in the FFA. Behavioral results revealed
    a wide distribution of face discrimination performance in ASD, ranging
    from typical performance to chance level performance. Despite this
    heterogeneity in perceptual abilities, individual face discrimination
    performance was well predicted by neural selectivity to faces in
    the FFA, estimated via both a novel analysis of local voxel-wise
    correlations, and the more commonly used fMRI rapid adaptation technique.
    Thus, face processing in ASD appears to rely on the FFA as in typical
    individuals, differing quantitatively but not qualitatively. These
    results for the first time mechanistically link variations in the
    ASD phenotype to specific differences in the typical face processing
    circuit, identifying promising targets for interventions.
    BibTeX:
    @article{Jiang2013,
      author = {Jiang, Xiong and Bollich, Angela and Cox, Patrick and Hyder, Eric and James, Joette and Gowani, Saqib Ali and Hadjikhani, Nouchine and Blanz, Volker and Manoach, Dara S. and Barton, Jason J S. and Gaillard, William D. and Riesenhuber, Maximilian},
      title = {A quantitative link between face discrimination deficits and neuronal selectivity for faces in autism.},
      journal = {Neuroimage Clin},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2013},
      volume = {2},
      pages = {320--331},
      url = {http://dx.doi.org/10.1016/j.nicl.2013.02.002},
      doi = {http://doi.org/10.1016/j.nicl.2013.02.002}
    }
    
    Karamzadeh, N., Medvedev, A., Azari, A., Gandjbakhche, A. & Najafizadeh, L. Capturing dynamic patterns of task-based functional connectivity with EEG. 2013 Neuroimage
    Vol. 66, pp. 311-317School: National Institutes of Health, NICHD, SAFB, Bethesda, MD, USA; Department of Electrical and Computer Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 
    DOI URL 
    Abstract: A new approach to trace the dynamic patterns of task-based functional
    connectivity, by combining signal segmentation, dynamic time warping
    (DTW), and Quality Threshold (QT) clustering techniques, is presented.
    Electroencephalography (EEG) signals of 5 healthy subjects were recorded
    as they performed an auditory oddball and a visual modified oddball
    tasks. To capture the dynamic patterns of functional connectivity
    during the execution of each task, EEG signals are segmented into
    durations that correspond to the temporal windows of previously well-studied
    event-related potentials (ERPs). For each temporal window, DTW is
    employed to measure the functional similarities among channels. Unlike
    commonly used temporal similarity measures, such as cross correlation,
    DTW compares time series by taking into consideration that their
    alignment properties may vary in time. QT clustering analysis is
    then used to automatically identify the functionally connected regions
    in each temporal window. For each task, the proposed approach was
    able to establish a unique sequence of dynamic pattern (observed
    in all 5 subjects) for brain functional connectivity.
    BibTeX:
    @article{Karamzadeh2013,
      author = {Karamzadeh, Nader and Medvedev, Andrei and Azari, Afrouz and Gandjbakhche, Amir and Najafizadeh, Laleh},
      title = {Capturing dynamic patterns of task-based functional connectivity with EEG.},
      journal = {Neuroimage},
      school = {National Institutes of Health, NICHD, SAFB, Bethesda, MD, USA; Department of Electrical and Computer Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, Bethesda, MD, USA.},
      year = {2013},
      volume = {66},
      pages = {311--317},
      url = {http://dx.doi.org/10.1016/j.neuroimage.2012.10.032},
      doi = {http://doi.org/10.1016/j.neuroimage.2012.10.032}
    }
    
    Lee, H.J., Wu, J., Chung, J. & Wrathall, J.R. SOX2 expression is upregulated in adult spinal cord after contusion injury in both oligodendrocyte lineage and ependymal cells. 2013 J Neurosci Res
    Vol. 91(2), pp. 196-210School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: The upregulation of genes normally associated with development may
    occur in the adult after spinal cord injury (SCI). To test this,
    we performed real-time RT-PCR array analysis of mouse spinal cord
    mRNAs comparing embryonic day (E)14.5 spinal cord with intact adult
    and adult cord 1 week after a clinically relevant standardized contusion
    SCI. We found significantly increased expression of a large number
    of neural development- and stem cell-associated genes after SCI.
    These included Sox2 (sex determining region Y-box 2), a transcription
    factor that regulates self-renewal and potency of embryonic neural
    stem cells and is one of only a few key factors needed to induce
    pluripotency. In adult spinal cord of Sox2-EGFP mice, Sox2-EGFP was
    found mainly in the ependymal cells of the central canal. After SCI,
    both mRNA and protein levels of Sox2 were significantly increased
    at and near the injury site. By 1 day, Sox2 was upregulated in NG2(+)
    oligodendrocyte progenitor cells (OPC) in the spared white matter.
    By 3 days, Sox2-EGFP ependymal cells had increased proliferation
    and begun to form multiple layers and clusters of cells in the central
    lesion zone of the cord. Expression of Sox2 by NG2(+) cells had declined
    by 1 week, but increased numbers of other Sox2-expressing cells persisted
    for at least 4 weeks after SCI in both mouse and rat models. Thus,
    SCI upregulates many genes associated with development and neural
    stem cells, including the key transcription factor Sox2, which is
    expressed in a pool of cells that persists for weeks after SCI.
    BibTeX:
    @article{Lee2013,
      author = {Lee, Hyun Joon and Wu, Junfang and Chung, Jumi and Wrathall, Jean R.},
      title = {SOX2 expression is upregulated in adult spinal cord after contusion injury in both oligodendrocyte lineage and ependymal cells.},
      journal = {J Neurosci Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {91},
      number = {2},
      pages = {196--210},
      url = {http://dx.doi.org/10.1002/jnr.23151},
      doi = {http://doi.org/10.1002/jnr.23151}
    }
    
    Lee, K.J., Queenan, B.N., Rozeboom, A.M., Bellmore, R., Lim, S.T., Vicini, S. & Pak, D.T.S. Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons. 2013 Neuron
    Vol. 77(1), pp. 99-114School: Physiology, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Network activity homeostatically alters synaptic efficacy to constrain
    neuronal output. However, it is unclear how such compensatory adaptations
    coexist with synaptic information storage, especially in established
    networks. Here, we report that in mature hippocampal neurons in vitro,
    network activity preferentially regulated excitatory synapses within
    the proximal dendrites of CA3 neurons. These homeostatic synapses
    exhibited morphological, functional, and molecular signatures of
    the specialized contacts between mossy fibers of dentate granule
    cells and thorny excrescences (TEs) of CA3 pyramidal neurons. In vivo
    TEs were also selectively and bidirectionally altered by chronic
    activity changes. TE formation required presynaptic synaptoporin
    and was suppressed by the activity-inducible kinase, Plk2. These
    results implicate the mossy fiber-TE synapse as an independently
    tunable gain control locus that permits efficacious homeostatic adjustment
    of mossy fiber-CA3 synapses, while preserving synaptic weights that
    may encode information elsewhere within the mature hippocampal circuit.
    BibTeX:
    @article{Lee2013a,
      author = {Lee, Kea Joo and Queenan, Bridget N. and Rozeboom, Aaron M. and Bellmore, Ryan and Lim, Seung T. and Vicini, Stefano and Pak, Daniel T S.},
      title = {Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons.},
      journal = {Neuron},
      school = { Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {77},
      number = {1},
      pages = {99--114},
      url = {http://dx.doi.org/10.1016/j.neuron.2012.10.033},
      doi = {http://doi.org/10.1016/j.neuron.2012.10.033}
    }
    
    Liao, G.-Y., Li, Y. & Xu, B. Ablation of TrkB expression in RGS9-2 cells leads to hyperphagic obesity. 2013 Mol Metab
    Vol. 2(4), pp. 491-497School: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA ; Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. 
    DOI URL 
    Abstract: Brain-derived neurotrophic factor (BDNF) and its cognate receptor,
    TrkB (tropomyosin receptor kinase B), are widely expressed in the
    brain where they regulate a wide variety of biological processes,
    including energy homeostasis. However, the specific population(s)
    of TrkB-expressing neurons through which BDNF governs energy homeostasis
    remain(s) to be determined. Using the Cre-loxP recombination system,
    we deleted the mouse TrkB gene in RGS9-2-expressing cells. In this
    mouse mutant, TrkB expression was abolished in several hypothalamic
    nuclei, including arcuate nucleus, dorsomedial hypothalamus, and
    lateral hypothalamus. TrkB expression was also abolished in a small
    number of cells in other brain regions, including the cerebral cortex
    and striatum. The mutant animals developed hyperphagic obesity with
    normal energy expenditure. Despite hyperglycemia under fed conditions,
    these animals exhibited normal fasting blood glucose levels and normal
    glucose tolerance. These results suggest that BDNF regulates energy
    homeostasis in part through TrkB-expressing neurons in the hypothalamus.
    BibTeX:
    @article{Liao2013,
      author = {Liao, Guey-Ying and Li, Yuqing and Xu, Baoji},
      title = {Ablation of TrkB expression in RGS9-2 cells leads to hyperphagic obesity.},
      journal = {Mol Metab},
      school = {Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA ; Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.},
      year = {2013},
      volume = {2},
      number = {4},
      pages = {491--497},
      url = {http://dx.doi.org/10.1016/j.molmet.2013.08.002},
      doi = {http://doi.org/10.1016/j.molmet.2013.08.002}
    }
    
    Lonskaya, I., Desforges, N.M., Hebron, M.L. & Moussa, C.E.-H. Ubiquitination increases parkin activity to promote autophagic α-synuclein clearance. 2013 PLoS One
    Vol. 8(12), pp. e83914School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC, United States of America. 
    DOI URL 
    Abstract: Parkinson's disease (PD) is a movement disorder associated with genetic
    and age related causes. Although autosomal recessive early onset
    PD linked to parkin mutations does not exhibit α-synuclein accumulation,
    while autosomal dominant and sporadic PD manifest with α-synuclein
    inclusions, loss of dopaminergic substantia nigra neurons is a common
    denominator in PD. Here we show that decreased parkin ubiquitination
    and loss of parkin stability impair interaction with Beclin-1 and
    alter α-synuclein degradation, leading to death of dopaminergic neurons.
    Tyrosine kinase inhibition increases parkin ubiquitination and interaction
    with Beclin-1, promoting autophagic α-synuclein clearance and nigral
    neuron survival. However, loss of parkin via deletion increases α-synuclein
    in the blood compared to the brain, suggesting that functional parkin
    prevents α-synuclein release into the blood. These studies demonstrate
    that parkin ubiquitination affects its protein stability and E3 ligase
    activity, possibly leading to α-synuclein sequestration and subsequent
    clearance.
    BibTeX:
    @article{Lonskaya2013a,
      author = {Lonskaya, Irina and Desforges, Nicole M. and Hebron, Michaeline L. and Moussa, Charbel E-H.},
      title = {Ubiquitination increases parkin activity to promote autophagic α-synuclein clearance.},
      journal = {PLoS One},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC, United States of America.},
      year = {2013},
      volume = {8},
      number = {12},
      pages = {e83914},
      url = {http://dx.doi.org/10.1371/journal.pone.0083914},
      doi = {http://doi.org/10.1371/journal.pone.0083914}
    }
    
    Lonskaya, I., Hebron, M.L., Desforges, N.M., Franjie, A. & Moussa, C.E.-H. Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance. 2013 EMBO Mol Med
    Vol. 5(8), pp. 1247-1262School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: Tyrosine kinase inhibitors (TKIs) are effective therapies for leukaemia.
    Alzheimer is a neurodegenerative disease characterized by accumulation
    of ?-amyloid (plaques) and hyper-phosphorylated Tau (tangles). Here
    we show that AD animals have high levels of insoluble parkin and
    decreased parkin-Beclin-1 interaction, while peripheral administration
    of TKIs, including Nilotinib and Bosutinib, increases soluble parkin
    leading to amyloid clearance and cognitive improvement. Blocking
    Beclin-1 expression with shRNA or parkin deletion prevents tyrosine
    kinase (TK) inhibition-induced amyloid clearance, suggesting that
    functional parkin-Beclin-1 interaction mediates amyloid degradation.
    Isolation of autophagic vacuoles (AVs) in AD mouse brain shows accumulation
    of parkin and amyloid, consistent with previous results in AD brains,
    while Bosutinib and Nilotinib increase parkin-Beclin-1 interaction
    and result in protein deposition in the lysosome. These data suggest
    that decreased parkin solubility impedes parkin-Beclin-1 interaction
    and amyloid clearance. We identified two FDA-approved anti-cancer
    drugs as potential treatment for AD.
    BibTeX:
    @article{Lonskaya2013c,
      author = {Lonskaya, Irina and Hebron, Michaeline L. and Desforges, Nicole M. and Franjie, Alexander and Moussa, Charbel E-H.},
      title = {Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance.},
      journal = {EMBO Mol Med},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2013},
      volume = {5},
      number = {8},
      pages = {1247--1262},
      url = {http://dx.doi.org/10.1002/emmm.201302771},
      doi = {http://doi.org/10.1002/emmm.201302771}
    }
    
    Lonskaya, I., Partridge, J., Lalchandani, R.R., Chung, A., Lee, T., Vicini, S., Hoe, H.-S., Lim, S.T. & Conant, K. Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1. 2013 PLoS One
    Vol. 8(7), pp. e69136School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America. 
    DOI URL 
    Abstract: Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases
    that can be released from neurons in an activity dependent manner
    to play a role in varied forms of learning and memory. MMP inhibitors
    impair hippocampal long term potentiation (LTP), spatial memory,
    and behavioral correlates of drug addiction. Since MMPs are thought
    to influence LTP through a ?1 integrin dependent mechanism, it has
    been suggested that these enzymes cleave specific substrates to generate
    integrin binding ligands. In previously published work, we have shown
    that neuronal activity stimulates rapid MMP dependent shedding of
    intercellular adhesion molecule-5 (ICAM-5), a synaptic adhesion molecule
    expressed on dendrites of the telencephalon. We have also shown that
    the ICAM-5 ectodomain can interact with ?1 integrins to stimulate
    integrin dependent phosphorylation of cofilin, an event that occurs
    with dendritic spine maturation and LTP. In the current study, we
    investigate the potential for the ICAM-5 ectodomain to stimulate
    changes in ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor
    (AMPAR) dependent glutamatergic transmission. Single cell recordings
    show that the ICAM-5 ectodomain stimulates an increase in the frequency,
    but not the amplitude, of AMPA mini excitatory post synaptic currents
    (mEPSCs). With biotinylation and precipitation assays, we also show
    that the ICAM-5 ectodomain stimulates an increase in membrane levels
    of GluA1, but not GluA2, AMPAR subunits. In addition, we observe
    an ICAM-5 associated increase in GluA1 phosphorylation at serine
    845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining
    along dendrites without affecting an increase in dendritic spine
    number. Together these data are consistent with the possibility that
    soluble ICAM-5 increases glutamatergic transmission and that post-synaptic
    changes, including increased phosphorylation and dendritic insertion
    of GluA1, could contribute. We suggest that future studies are warranted
    to determine whether ICAM-5 is one of a select group of synaptic
    CAMs whose shedding contributes to MMP dependent effects on learning
    and memory.
    BibTeX:
    @article{Lonskaya2013b,
      author = {Lonskaya, Irina and Partridge, John and Lalchandani, Rupa R. and Chung, Andrew and Lee, Taehee and Vicini, Stefano and Hoe, Hyang-Sook and Lim, Seung T. and Conant, Katherine},
      title = {Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1.},
      journal = {PLoS One},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America.},
      year = {2013},
      volume = {8},
      number = {7},
      pages = {e69136},
      url = {http://dx.doi.org/10.1371/journal.pone.0069136},
      doi = {http://doi.org/10.1371/journal.pone.0069136}
    }
    
    Lonskaya, I., Shekoyan, A.R., Hebron, M.L., Desforges, N., Algarzae, N.K. & Moussa, C.E.-H. Diminished parkin solubility and co-localization with intraneuronal amyloid-β are associated with autophagic defects in Alzheimer's disease. 2013 J Alzheimers Dis
    Vol. 33(1), pp. 231-247School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Alzheimer's disease (AD) is an aging disorder characterized by amyloid-β
    (AΒ) accumulation in extracellular plaques and formation of intracellular
    tangles containing hyperphosphorylated tau (p-Tau). Autophagic defects,
    leading to accumulation of autophagosomes, are recognized in AD.
    Parkin is an E3 ubiquitin ligase involved in degradation of proteins
    via autophagy and the proteasome. We investigated the role of parkin
    in postmortem brain tissues from 21 AD patients and 15 control subjects.
    We detected decreased parkin solubility in AD cortex and parkin co-localization
    with intraneuronal AΒ(1-42) in the hippocampus and cortex of AD patients.
    Parkin accumulation with intraneuronal AΒ and p-Tau was detected
    in autophagosomes in AD brains. To determine the role of parkin in
    AΒ clearance, we generated gene transfer animals expressing lentiviral
    AΒ(1-42)with and without parkin and examined autophagic mechanisms.
    Lentiviral expression of AΒ(1-42) led to p-Tau accumulation and induced
    autophagic defects, leading to accumulation of autophagic vacuoles.
    However, co-expression of wild type parkin facilitated autophagic
    clearance and promoted deposition of AΒ(1-42) and p-Tau into the
    lysosome. Taken together, these data suggest that AΒ(1-42) alters
    normal autophagy and parkin enhances autophagic clearance. In conclusion,
    decreased parkin solubility may lead to co-localization with intraneuronal
    AΒ(1-42) and compromise the cell autophagic clearance ability. Parkin
    may clear autophagic defects via autophagosome degradation.
    BibTeX:
    @article{Lonskaya2013,
      author = {Lonskaya, Irina and Shekoyan, Ashot R. and Hebron, Michaeline L. and Desforges, Nicole and Algarzae, Norah K. and Moussa, Charbel E-H.},
      title = {Diminished parkin solubility and co-localization with intraneuronal amyloid-β are associated with autophagic defects in Alzheimer's disease.},
      journal = {J Alzheimers Dis},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {33},
      number = {1},
      pages = {231--247},
      url = {http://dx.doi.org/10.3233/JAD-2012-121141},
      doi = {http://doi.org/10.3233/JAD-2012-121141}
    }
    
    Mocchetti, I., Campbell, L.A., Harry, G.J. & Avdoshina, V. When human immunodeficiency virus meets chemokines and microglia: neuroprotection or neurodegeneration? 2013 J Neuroimmune Pharmacol
    Vol. 8(1), pp. 118-131School: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, Washington, DC, 20057, USA, moccheti@georgetown.edu. 
    DOI URL 
    Abstract: Chemokines are chemotactic cytokines that were originally discovered
    as promoters of leukocyte proliferation and mobility. In recent years,
    however, evidence has demonstrated constitutive expression of chemokines
    and chemokine receptors in a variety of cells in the central and
    peripheral nervous system and has proposed a role for chemokines
    in neurodegenerative diseases characterized by inflammation and microglia
    proliferation. In addition, chemokine receptors, and in particular
    CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV)
    infection of immunocompetent cells as well as microglia. Subsequently,
    HIV, through a variety of mechanisms, promotes synapto-dendritic
    alterations and neuronal loss that ultimately lead to motor and cognitive
    impairments. These events are accompanied by microglia activation.
    Nevertheless, a microglia-mediated mechanism of neuronal degeneration
    alone cannot fully explain some of the pathological features of HIV
    infected brain such as synaptic simplification. In this article,
    we present evidence that some of the microglia responses to HIV are
    beneficial and neuroprotective. These include the ability of microglia
    to release anti-inflammatory cytokines, to remove dying cells and
    to promote axonal sprouting.
    BibTeX:
    @article{Mocchetti2013,
      author = {Mocchetti, Italo and Campbell, Lee A. and Harry, G Jean and Avdoshina, Valeriya},
      title = {When human immunodeficiency virus meets chemokines and microglia: neuroprotection or neurodegeneration?},
      journal = {J Neuroimmune Pharmacol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, Washington, DC, 20057, USA, moccheti@georgetown.edu.},
      year = {2013},
      volume = {8},
      number = {1},
      pages = {118--131},
      url = {http://dx.doi.org/10.1007/s11481-012-9353-4},
      doi = {http://doi.org/10.1007/s11481-012-9353-4}
    }
    
    Neckel, N.D., Dai, H. & Bregman, B.S. Quantifying changes following spinal cord injury with velocity dependent locomotor measures. 2013 J Neurosci Methods
    Vol. 214(1), pp. 27-36School: Department of Neuroscience, Georgetown University Medical Center, Washington 20007, DC, USA. Electronic address: ndn3@georgetown.edu. 
    DOI URL 
    Abstract: Many locomotor measures commonly used to assess functional deficits
    following neurological injury are velocity dependent. This makes
    the comparison of faster pre-injury walking to slower post-injury
    walking a challenging process. In lieu of calculating mean values
    at specific velocities, we have employed the use of nonlinear regression
    techniques to quantify locomotor measures across all velocities.
    This enables us to assess more accurately the locomotor recovery
    of rats after a cervical spinal cord injury. For example, while the
    mean stride length of the hindlimbs decreased following injury, regression
    analysis revealed that the change was due to the reduction in walking
    speed and not a functional deficit. A significant difference in the
    percent of the right forelimb step cycle that was spent in stance
    phase, or duty factor, was found across all velocities, however this
    deficit spontaneously recovered after 6 weeks. Conversely, no differences
    were initially found in hindlimb stride length, but abnormal compensatory
    techniques were found to have developed 3 weeks after injury.
    BibTeX:
    @article{Neckel2013,
      author = {Neckel, Nathan D. and Dai, Haining and Bregman, Barbara S.},
      title = {Quantifying changes following spinal cord injury with velocity dependent locomotor measures.},
      journal = {J Neurosci Methods},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington 20007, DC, USA. Electronic address: ndn3@georgetown.edu.},
      year = {2013},
      volume = {214},
      number = {1},
      pages = {27--36},
      url = {http://dx.doi.org/10.1016/j.jneumeth.2013.01.008},
      doi = {http://doi.org/10.1016/j.jneumeth.2013.01.008}
    }
    
    Niedringhaus, M., Chen, X., Conant, K. & Dzakpasu, R. Synaptic Potentiation Facilitates Memory-like Attractor Dynamics in Cultured In Vitro Hippocampal Networks. 2013 PLoS One
    Vol. 8(3), pp. e57144School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America. 
    DOI URL 
    Abstract: Collective rhythmic dynamics from neurons is vital for cognitive functions
    such as memory formation but how neurons self-organize to produce
    such activity is not well understood. Attractor-based computational
    models have been successfully implemented as a theoretical framework
    for memory storage in networks of neurons. Additionally, activity-dependent
    modification of synaptic transmission is thought to be the physiological
    basis of learning and memory. The goal of this study is to demonstrate
    that using a pharmacological treatment that has been shown to increase
    synaptic strength within in vitro networks of hippocampal neurons
    follows the dynamical postulates theorized by attractor models. We
    use a grid of extracellular electrodes to study changes in network
    activity after this perturbation and show that there is a persistent
    increase in overall spiking and bursting activity after treatment.
    This increase in activity appears to recruit more "errant" spikes
    into bursts. Phase plots indicate a conserved activity pattern suggesting
    that a synaptic potentiation perturbation to the attractor leaves
    it unchanged. Lastly, we construct a computational model to demonstrate
    that these synaptic perturbations can account for the dynamical changes
    seen within the network.
    BibTeX:
    @article{Niedringhaus2013,
      author = {Niedringhaus, Mark and Chen, Xin and Conant, Katherine and Dzakpasu, Rhonda},
      title = {Synaptic Potentiation Facilitates Memory-like Attractor Dynamics in Cultured In Vitro Hippocampal Networks.},
      journal = {PLoS One},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America.},
      year = {2013},
      volume = {8},
      number = {3},
      pages = {e57144},
      url = {http://dx.doi.org/10.1371/journal.pone.0057144},
      doi = {http://doi.org/10.1371/journal.pone.0057144}
    }
    
    North, H.A., Clifford, M.A. & Donoghue, M.J. 'Til Eph do us part': intercellular signaling via Eph receptors and ephrin ligands guides cerebral cortical development from birth through maturation. 2013 Cereb Cortex
    Vol. 23(8), pp. 1765-1773School: Department of Biology and The Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Eph receptors, the largest family of surface-bound receptor tyrosine
    kinases and their ligands, the ephrins, mediate a wide variety of
    cellular interactions in most organ systems throughout both development
    and maturity. In the forming cerebral cortex, Eph family members
    are broadly and dynamically expressed in particular sets of cortical
    cells at discrete times. Here, we review the known functions of Eph-mediated
    intercellular signaling in the generation of progenitors, the migration
    of maturing cells, the differentiation of neurons, the formation
    of functional connections, and the choice between life and death
    during corticogenesis. In synthesizing these results, we posit a
    signaling paradigm in which cortical cells maintain a life history
    of Eph-mediated intercellular interactions that guides subsequent
    cellular decision-making.
    BibTeX:
    @article{North2013,
      author = {North, Hilary A. and Clifford, Meredith A. and Donoghue, Maria J.},
      title = {'Til Eph do us part': intercellular signaling via Eph receptors and ephrin ligands guides cerebral cortical development from birth through maturation.},
      journal = {Cereb Cortex},
      school = {Department of Biology and The Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20057, USA.},
      year = {2013},
      volume = {23},
      number = {8},
      pages = {1765--1773},
      url = {http://dx.doi.org/10.1093/cercor/bhs183},
      doi = {http://doi.org/10.1093/cercor/bhs183}
    }
    
    Noto, C.T., Mahzar, S., Gnadt, J. & Kanwal, J.S. A flexible user-interface for audiovisual presentation and interactive control in neurobehavioral experiments. 2013 F1000Res
    Vol. 2, pp. 20School: Department of Neurology, Georgetown University, Washington DC, 20057, USA ; Department of Physiology and Biophysics, Georgetown University, Washington DC, 20057, USA. 
    DOI URL 
    Abstract: A major problem facing behavioral neuroscientists is a lack of unified,
    vendor-distributed data acquisition systems that allow stimulus presentation
    and behavioral monitoring while recording neural activity. Numerous
    systems perform one of these tasks well independently, but to our
    knowledge, a useful package with a straightforward user interface
    does not exist. Here we describe the development of a flexible, script-based
    user interface that enables customization for real-time stimulus
    presentation, behavioral monitoring and data acquisition. The experimental
    design can also incorporate neural microstimulation paradigms. We
    used this interface to deliver multimodal, auditory and visual (images
    or video) stimuli to a nonhuman primate and acquire single-unit data.
    Our design is cost-effective and works well with commercially available
    hardware and software. Our design incorporates a script, providing
    high-level control of data acquisition via a sequencer running on
    a digital signal processor to enable behaviorally triggered control
    of the presentation of visual and auditory stimuli. Our experiments
    were conducted in combination with eye-tracking hardware. The script,
    however, is designed to be broadly useful to neuroscientists who
    may want to deliver stimuli of different modalities using any animal
    model.
    BibTeX:
    @article{Noto2013,
      author = {Noto, Christopher T. and Mahzar, Suleman and Gnadt, James and Kanwal, Jagmeet S.},
      title = {A flexible user-interface for audiovisual presentation and interactive control in neurobehavioral experiments.},
      journal = {F1000Res},
      school = {Department of Neurology, Georgetown University, Washington DC, 20057, USA ; Department of Physiology and Biophysics, Georgetown University, Washington DC, 20057, USA.},
      year = {2013},
      volume = {2},
      pages = {20},
      url = {http://dx.doi.org/10.12688/f1000research.2-20.v2},
      doi = {http://doi.org/10.12688/f1000research.2-20.v2}
    }
    
    Olulade, O.A., Flowers, D.L., Napoliello, E.M. & Eden, G.F. Developmental differences for word processing in the ventral stream. 2013 Brain Lang
    Vol. 125(2), pp. 134-145School: Center for the Study of Learning, Georgetown University Medical Center, 4000 Reservoir Road NW, Building D, Suite 150, Washington, DC 20057, USA. oao24@georgetown.edu 
    DOI URL 
    Abstract: The visual word form system (VWFS), located in the occipito-temporal
    cortex, is involved in orthographic processing of visually presented
    words (Cohen et al., 2002). Recent fMRI studies in children and adults
    have demonstrated a gradient of increasing word-selectivity along
    the posterior-to-anterior axis of this system (Vinckier et al., 2007),
    yet whether this pattern is modified by the increased reading experience
    afforded by age is still in question. In this study, we employed
    fMRI and an implicit word-processing task, and then used a region
    of interest analysis approach along the occipito-temporal cortex
    to test the prediction that the selectivity for words along the extent
    of the VWFS differs between older experienced and younger novice
    readers. Our results showed differences between children and adults
    during word processing in the anterior left occipito-temporal cortex,
    providing evidence of developmental refinement for word recognition
    along the VWFS.
    BibTeX:
    @article{Olulade2013,
      author = {Olulade, Olumide A. and Flowers, D Lynn and Napoliello, Eileen M. and Eden, Guinevere F.},
      title = {Developmental differences for word processing in the ventral stream.},
      journal = {Brain Lang},
      school = {Center for the Study of Learning, Georgetown University Medical Center, 4000 Reservoir Road NW, Building D, Suite 150, Washington, DC 20057, USA. oao24@georgetown.edu},
      year = {2013},
      volume = {125},
      number = {2},
      pages = {134--145},
      url = {http://dx.doi.org/10.1016/j.bandl.2012.04.003},
      doi = {http://doi.org/10.1016/j.bandl.2012.04.003}
    }
    
    Rodriguez, G.A., Burns, M.P., Weeber, E.J. & Rebeck, G.W. Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex. 2013 Learn Mem
    Vol. 20(5), pp. 256-266School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: The apolipoprotein E4 (APOE-?4) allele is the strongest genetic risk
    factor for developing late-onset Alzheimer's disease, and may predispose
    individuals to Alzheimer's-related cognitive decline by affecting
    normal brain function early in life. To investigate the impact of
    human APOE alleles on cognitive performance in mice, we trained 3-mo-old
    APOE targeted replacement mice (E2, E3, and E4) in the Barnes maze
    to locate and enter a target hole along the perimeter of the maze.
    Long-term spatial memory was probed 24 h and 72 h after training.
    We found that young E4 mice exhibited significantly impaired spatial
    learning and memory in the Barnes maze compared to E3 mice. Deficits
    in spatial cognition were also present in a second independent cohort
    of E4 mice tested at 18 mo of age. In contrast, cognitive performance
    in the hidden platform water maze was not as strongly affected by
    APOE genotype. We also examined the dendritic morphology of neurons
    in the medial entorhinal cortex of 3-mo-old TR mice, neurons important
    to spatial learning functions. We found significantly shorter dendrites
    and lower spine densities in basal shaft dendrites of E4 mice compared
    to E3 mice, consistent with spatial learning and memory deficits
    in E4 animals. These findings suggest that human APOE-?4 may affect
    cognitive function and neuronal morphology early in life.
    BibTeX:
    @article{Rodriguez2013,
      author = {Rodriguez, Gustavo A. and Burns, Mark P. and Weeber, Edwin J. and Rebeck, G William},
      title = {Young APOE4 targeted replacement mice exhibit poor spatial learning and memory, with reduced dendritic spine density in the medial entorhinal cortex.},
      journal = {Learn Mem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {20},
      number = {5},
      pages = {256--266},
      url = {http://dx.doi.org/10.1101/lm.030031.112},
      doi = {http://doi.org/10.1101/lm.030031.112}
    }
    
    Sohn, Y.I., Lee, N.J., Chung, A., Saavedra, J.M., Scott Turner, R., Pak, D.T.S. & Hoe, H.-S. Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking. 2013 Biochem Biophys Res Commun
    Vol. 439(4), pp. 464-470School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Recent studies demonstrated that the antihypertensive drug Valsartan
    improved spatial and episodic memory in mouse models of Alzheimer's
    Disease (AD) and human subjects with hypertension. However, the molecular
    mechanism by which Valsartan can regulate cognitive function is still
    unknown. Here, we investigated the effect of Valsartan on dendritic
    spine formation in primary hippocampal neurons, which is correlated
    with learning and memory. Interestingly, we found that Valsartan
    promotes spinogenesis in developing and mature neurons. In addition,
    we found that Valsartan increases the puncta number of PSD-95 and
    trends toward an increase in the puncta number of synaptophysin.
    Moreover, Valsartan increased the cell surface levels of AMPA receptors
    and selectively altered the levels of spinogenesis-related proteins,
    including CaMKII? and phospho-CDK5. These data suggest that Valsartan
    may promote spinogenesis by enhancing AMPA receptor trafficking and
    synaptic plasticity signaling.
    BibTeX:
    @article{Sohn2013,
      author = {Sohn, Young In and Lee, Nathanael J. and Chung, Andrew and Saavedra, Juan M. and Scott Turner, R. and Pak, Daniel T S. and Hoe, Hyang-Sook},
      title = {Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking.},
      journal = {Biochem Biophys Res Commun},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2013},
      volume = {439},
      number = {4},
      pages = {464--470},
      url = {http://dx.doi.org/10.1016/j.bbrc.2013.08.091},
      doi = {http://doi.org/10.1016/j.bbrc.2013.08.091}
    }
    
    Sung, Y.M., Lee, T., Yoon, H., DiBattista, A.M., Song, J.M., Sohn, Y., Moffat, E.I., Turner, R.S., Jung, M., Kim, J. & Hoe, H.-S. Mercaptoacetamide-based class II HDAC inhibitor lowers AΒ levels and improves learning and memory in a mouse model of Alzheimer's disease. 2013 Exp Neurol
    Vol. 239, pp. 192-201School: Department of Neuroscience, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Histone deacetylase inhibitors (HDACIs) alter gene expression epigenetically
    by interfering with the normal functions of HDAC. Given their ability
    to decrease AΒ levels, HDACIs are a potential treatment for Alzheimer's
    disease (AD). However, it is unclear how HDACIs alter AΒ levels.
    We developed two novel HDAC inhibitors with improved pharmacological
    properties, such as a longer half-life and greater penetration of
    the blood-brain barrier: mercaptoacetamide-based class II HDACI (coded
    as W2) and hydroxamide-based class I and IIHDACI (coded as I2) and
    investigated how they affect AΒ levels and cognition. HDACI W2 decreased
    AΒ40 and AΒ42 in vitro. HDACI I2 also decreased AΒ40, but not AΒ42.
    We systematically examined the molecular mechanisms by which HDACIs
    W2 and I2 can decrease AΒ levels. HDACI W2 decreased gene expression
    of ?-secretase components and increased the AΒ degradation enzyme
    Mmp2. Similarly, HDACI I2 decreased expression of ?- and ?-secretase
    components and increased mRNA levels of AΒ degradation enzymes. HDACI
    W2 also significantly decreased AΒ levels and rescued learning and
    memory deficits in aged hAPP 3xTg AD mice. Furthermore, we found
    that the novel HDACI W2 decreased tau phosphorylation at Thr181,
    an effect previously unknown for HDACIs. Collectively, these data
    suggest that class II HDACls may serve as a novel therapeutic strategy
    for AD.
    BibTeX:
    @article{Sung2013,
      author = {Sung, You Me and Lee, Taehee and Yoon, Hyejin and DiBattista, Amanda Marie and Song, Jung Min and Sohn, Yoojin and Moffat, Emily Isabella and Turner, R Scott and Jung, Mira and Kim, Jungsu and Hoe, Hyang-Sook},
      title = {Mercaptoacetamide-based class II HDAC inhibitor lowers AΒ levels and improves learning and memory in a mouse model of Alzheimer's disease.},
      journal = {Exp Neurol},
      school = {Department of Neuroscience, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA.},
      year = {2013},
      volume = {239},
      pages = {192--201},
      url = {http://dx.doi.org/10.1016/j.expneurol.2012.10.005},
      doi = {http://doi.org/10.1016/j.expneurol.2012.10.005}
    }
    
    Tai, A.X., Cassidy, R.M. & Kromer, L.F. EphA7 expression identifies a unique neuronal compartment in the rat striatum. 2013 J Comp NeurolSchool: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.  DOI URL 
    Abstract: Prior studies have identified two anatomically and neurochemically
    distinct cellular compartments within the mammalian striatum, termed
    striosomes and matrix, which express ?-opioid receptors (?OR) and
    EphA4, respectively. Here we identify and characterize an additional
    compartment in the rat striatum composed of neurons that express
    EphA7. In situ hybridization and immunohistochemical data indicate
    that neurons expressing EphA7 mRNA and protein are arranged in a
    banded "matrisome-like" pattern confined to the matrix in the dorsal
    striatum. Within the ventral striatum, EphA7-positive (+) neurons
    have a less organized mosaic pattern that partially overlaps areas
    expressing ?OR. Immunolabeling data demonstrate that EphA7(+) striatofugal
    axons form distinct fascicles leaving the striatum. Within the globus
    pallidus, EphA7(+) axons terminate primarily within ventromedial
    areas of the nucleus and along its striatal border. EphA7(+) axons
    avoid regions containing dopamine neurons within the substantia nigra
    and preferentially innervate areas near the rostral and caudal margins
    of the nucleus. Within both nuclei, EphA7(+) axons have similar but
    more restricted terminal fields than the entire population of EphA4(+)
    matrix axons, indicating that EphA7(+) axons comprise a subpopulation
    of matrix axons. Ligand binding data demonstrate that ephrin-A5 selectively
    binds areas of the striatum, globus pallidus and substantia nigra
    containing EphA7(+) neurons and axons, but not areas expressing only
    EphA4. Our findings demonstrate that EphA7 expression identifies
    a novel "matrisome" compartment within the matrix that binds ephrin-A5
    and possesses unique axonal projections. Our findings also suggest
    that EphA7 and ephrin-A5 may participate in the formation of this
    matrisome subcompartment and its striatofugal projections. J. Comp.
    Neurol., 2013. © 2013 Wiley Periodicals, Inc.
    BibTeX:
    @article{Tai2013,
      author = {Tai, Alexander X. and Cassidy, Robert M. and Kromer, Lawrence F.},
      title = {EphA7 expression identifies a unique neuronal compartment in the rat striatum.},
      journal = {J Comp Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2013},
      url = {http://dx.doi.org/10.1002/cne.23308},
      doi = {http://doi.org/10.1002/cne.23308}
    }
    
    Tian, B., Ku?mierek, P. & Rauschecker, J.P. Analogues of simple and complex cells in rhesus monkey auditory cortex. 2013 Proc Natl Acad Sci U S A
    Vol. 110(19), pp. 7892-7897School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1460, USA. 
    DOI URL 
    Abstract: Receptive fields (RFs) of neurons in primary visual cortex have traditionally
    been subdivided into two major classes: "simple" and "complex" cells.
    Simple cells were originally defined by the existence of segregated
    subregions within their RF that respond to either the on- or offset
    of a light bar and by spatial summation within each of these regions,
    whereas complex cells had ON and OFF regions that were coextensive
    in space [Hubel DH, et al. (1962) J Physiol 160:106-154]. Although
    other definitions based on the linearity of response modulation have
    been proposed later [Movshon JA, et al. (1978) J Physiol 283:53-77;
    Skottun BC, et al. (1991) Vision Res 31(7-8):1079-1086], the segregation
    of ON and OFF subregions has remained an important criterion for
    the distinction between simple and complex cells. Here we report
    that response profiles of neurons in primary auditory cortex of monkeys
    show a similar distinction: one group of cells has segregated ON
    and OFF subregions in frequency space; and another group shows ON
    and OFF responses within largely overlapping response profiles. This
    observation is intriguing for two reasons: (i) spectrotemporal dissociation
    in the auditory domain provides a basic neural mechanism for the
    segregation of sounds, a fundamental prerequisite for auditory figure-ground
    discrimination; and (ii) the existence of similar types of RF organization
    in visual and auditory cortex would support the existence of a common
    canonical processing algorithm within cortical columns.
    BibTeX:
    @article{Tian2013,
      author = {Tian, Biao and Ku?mierek, Pawe? and Rauschecker, Josef P.},
      title = {Analogues of simple and complex cells in rhesus monkey auditory cortex.},
      journal = {Proc Natl Acad Sci U S A},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1460, USA.},
      year = {2013},
      volume = {110},
      number = {19},
      pages = {7892--7897},
      url = {http://dx.doi.org/10.1073/pnas.1221062110},
      doi = {http://doi.org/10.1073/pnas.1221062110}
    }
    
    West, E.A., Forcelli, P.A., McCue, D.L. & Malkova, L. Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats. 2013 Behav Brain Res
    Vol. 246C, pp. 10-14School: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, United States; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007, United States. Electronic address: WestE@email.unc.edu. 
    DOI URL 
    Abstract: The orbitofrontal cortex (OFC) is critical for behavioral adaptation
    in response to changes in reward value. Here we investigated, in
    rats, the role of OFC and, specifically, serotonergic neurotransmission
    within OFC in a reinforcer devaluation task (which measures behavioral
    flexibility). This task used two visual cues, each predicting one
    of two foods, with the spatial position (left-right) of the cues
    above two levers pseudorandomized across trials. An instrumental
    action (lever press) was required for reinforcer delivery. After
    training, rats received either excitotoxic OFC lesions made by NMDA
    (N-methyl-d-aspartic acid), serotonin-specific OFC lesions made by
    5,7-DHT (5,7-dihydroxytryptamine), or sham lesions. In sham-lesioned
    rats, devaluation of one food (by feeding to satiety) significantly
    decreased responding to the cue associated with that food, when both
    cues were presented simultaneously during extinction. Both types
    of OFC lesions disrupted the devaluation effect. In contrast, extinction
    learning was not affected by serotonin-specific lesions and was only
    mildly retarded in rats with excitotoxic lesions. Thus, serotonin
    within OFC is necessary for appropriately adjusting behavior toward
    cues that predict reward but not for reducing responses in the absence
    of reward. Our results are the first to demonstrate that serotonin
    in OFC is necessary for reinforcer devaluation, but not extinction.
    BibTeX:
    @article{West2013,
      author = {West, Elizabeth A. and Forcelli, Patrick A. and McCue, David L. and Malkova, Ludise},
      title = {Differential effects of serotonin-specific and excitotoxic lesions of OFC on conditioned reinforcer devaluation and extinction in rats.},
      journal = {Behav Brain Res},
      school = {Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, United States; Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20007, United States. Electronic address: WestE@email.unc.edu.},
      year = {2013},
      volume = {246C},
      pages = {10--14},
      url = {http://dx.doi.org/10.1016/j.bbr.2013.02.027},
      doi = {http://doi.org/10.1016/j.bbr.2013.02.027}
    }
    
    Winston, C.N., Chellappa, D., Wilkins, T., Barton, D.J., Washington, P.M., Loane, D.J., Zapple, D.N. & Burns, M.P. Controlled cortical impact results in an extensive loss of dendritic spines that is not mediated by injury-induced amyloid-beta accumulation. 2013 J Neurotrauma
    Vol. 30(23), pp. 1966-1972School: 1 Department of Neuroscience, Laboratory for Brain Injury and Dementia, Georgetown University Medical Center , Washington, DC. 
    DOI URL 
    Abstract: The clinical manifestations that occur after traumatic brain injury
    (TBI) include a wide range of cognitive, emotional, and behavioral
    deficits. The loss of excitatory synapses could potentially explain
    why such diverse symptoms occur after TBI, and a recent preclinical
    study has demonstrated a loss of dendritic spines, the postsynaptic
    site of the excitatory synapse, after fluid percussion injury. The
    objective of this study was to determine if controlled cortical impact
    (CCI) also resulted in dendritic spine retraction and to probe the
    underlying mechanisms of this spine loss. We used a unilateral CCI
    and visualized neurons and dendtritic spines at 24 h post-injury
    using Golgi stain. We found that TBI caused a 32% reduction of dendritic
    spines in layer II/III of the ipsilateral cortex and a 20% reduction
    in the dendritic spines of the ipsilateral dentate gyrus. Spine loss
    was not restricted to the ipsilateral hemisphere, however, with similar
    reductions in spine numbers recorded in the contralateral cortex
    (25% reduction) and hippocampus (23% reduction). Amyloid-β (AΒ),
    a neurotoxic peptide commonly associated with Alzheimer disease,
    accumulates rapidly after TBI and is also known to cause synaptic
    loss. To determine if AΒ contributes to spine loss after brain injury,
    we administered a ?-secretase inhibitor LY450139 after TBI. We found
    that while LY450139 administration could attenuate the TBI-induced
    increase in AΒ, it had no effect on dendritic spine loss after TBI.
    We conclude that the acute, global loss of dendritic spines after
    TBI is independent of ?-secretase activity or TBI-induced AΒ accumulation.
    BibTeX:
    @article{Winston2013,
      author = {Winston, Charisse N. and Chellappa, Deepa and Wilkins, Tiffany and Barton, David J. and Washington, Patricia M. and Loane, David J. and Zapple, David N. and Burns, Mark P.},
      title = {Controlled cortical impact results in an extensive loss of dendritic spines that is not mediated by injury-induced amyloid-beta accumulation.},
      journal = {J Neurotrauma},
      school = {1 Department of Neuroscience, Laboratory for Brain Injury and Dementia, Georgetown University Medical Center , Washington, DC.},
      year = {2013},
      volume = {30},
      number = {23},
      pages = {1966--1972},
      url = {http://dx.doi.org/10.1089/neu.2013.2960},
      doi = {http://doi.org/10.1089/neu.2013.2960}
    }
    
    Algarzae, N., Hebron, M., Miessau, M. & Moussa, C.E.-H. Parkin prevents cortical atrophy and AΒ-induced alterations of brain metabolism: ??C NMR and magnetic resonance imaging studies in AD models. 2012 Neuroscience
    Vol. 225, pp. 22-34School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Alzheimer's disease (AD) is a neurodegenerative aging disorder characterized
    by extracellular AΒ plaques and intraneuronal neurofibrillary tangles.
    We conducted longitudinal studies to examine the effects of AΒ on
    brain amino acid metabolism in lentiviral AΒ(1-42) gene transfer
    animals and transgenic AD mice. We also performed lentiviral parkin
    gene delivery to determine the effects of AΒ clearance in AD models.
    AΒ(1-42) activated mTOR signaling, and increased 4E-BP phosphorylation.
    AΒ(1-42) increased the synthesis of glutamate and aspartate, but
    not glutamine, leucine and isoleucine, but an increase in leucine
    and isoleucine levels was concurrent with diminution of neurotransmitters.
    Additionally, AΒ(1-42) attenuated mitochondrial tricarboxylic acid
    (TCA) cycle activity and decreased synthesis of its by-products.
    Glutamate levels increased prior to lactate accumulation, suggesting
    oxidative stress. Importantly, parkin reversed the effects of AΒ(1-42)
    on amino acid levels, prevented TCA cycle impairment and protected
    against glutamate toxicity. Cortical atrophy was observed in aged
    3xTg-AD mice, while parkin expression was associated with reduced
    atrophy. Similarly, AΒ(1-42) resulted in significant cell loss, pronounced
    astrogliosis and cortical atrophy and parkin reduced astrogliosis
    and reversed AΒ(1-42) effects on cell loss and cortical atrophy.
    Taken together these data suggest that parkin prevents amyloid-induced
    alteration of brain metabolism and may be used as a therapeutic target
    to limit neuronal loss in AD.
    BibTeX:
    @article{Algarzae2012,
      author = {Algarzae, Norah and Hebron, Michaeline and Miessau, Matthew and Moussa, Charbel E-H.},
      title = {Parkin prevents cortical atrophy and AΒ-induced alterations of brain metabolism: ??C NMR and magnetic resonance imaging studies in AD models.},
      journal = {Neuroscience},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2012},
      volume = {225},
      pages = {22--34},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2012.08.057},
      doi = {http://doi.org/10.1016/j.neuroscience.2012.08.057}
    }
    
    Béraud, D. & Maguire-Zeiss, K.A. Misfolded A$-synuclein and Toll-like receptors: therapeutic targets for Parkinson's disease. 2012 Parkinsonism Relat Disord
    Vol. 18 Suppl 1, pp. S17-S20School: Department of Neurostience and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Parkinson's disease (PD) is typified by the loss of midbrain dopamine
    neurons, the presence of large proteinaceous α-synuclein-positive
    intracellular inclusions, oxidatively modified molecules and activated
    microglia. The etiology of sporadic PD is not fully understood but
    several lines of evidence suggest that genetic vulnerability and
    environmental toxicants converge to incite pathology-the multiple
    hit hypothesis. One gene linked to both familial and sporadic PD
    is SNCA, which encodes for the protein a-synuclein that has a propensity
    to misfold into toxic moieties. Here we show that a-synuclein directly
    activates microglia inciting the production of proinflammatory molecules
    and altering the expression of Toll-like receptors (TLRs). We discuss
    the role for α-synuclein-directed TLR expression changes in PD and
    the therapeutic potential of modifying this response.
    BibTeX:
    @article{Beraud2012,
      author = {Béraud, Dawn and Maguire-Zeiss, Kathleen A.},
      title = {Misfolded A$-synuclein and Toll-like receptors: therapeutic targets for Parkinson's disease.},
      journal = {Parkinsonism Relat Disord},
      school = {Department of Neurostience and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2012},
      volume = {18 Suppl 1},
      pages = {S17--S20},
      url = {http://dx.doi.org/10.1016/S1353-8020(11)70008-6},
      doi = {http://doi.org/10.1016/S1353-8020(11)70008-6}
    }
    
    Bachis, A., Avdoshina, V., Zecca, L., Parsadanian, M. & Mocchetti, I. Human immunodeficiency virus type 1 alters brain-derived neurotrophic factor processing in neurons. 2012 J Neurosci
    Vol. 32(28), pp. 9477-9484School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057 and CNR Institute of Biomedical Technologies, 20090 Segrate, Italy. 
    DOI URL 
    Abstract: The molecular mechanisms leading to synaptic simplification and neuronal
    apoptosis in human immunodeficiency virus type 1 (HIV-1)-positive
    subjects are unknown. The HIV protein gp120 reduced the length of
    neuronal processes similarly to the proneurotrophin pro-brain-derived
    neurotrophic factor (proBDNF). Intriguingly, the effects of both
    proBDNF and gp120 were blocked by inhibitors of the p75 neurotrophin
    receptor, suggesting that proBDNF and gp120 share a similar mechanism
    of neurotoxicity. Therefore, we tested the hypothesis that gp120
    affects the release of proBDNF. Using rat primary neurons, we observed
    that gp120 promotes a time-dependent intracellular and extracellular
    accumulation of proBDNF concomitantly with a decrease in mature BDNF.
    A similar imbalance in the ratio proBDNF/mature BDNF was confirmed
    in postmortem brains of HIV-positive subjects cognitively impaired
    and motor impaired. Therefore, it is conceivable to formulate the
    hypothesis that HIV neurotoxicity includes a gp120-mediated alteration
    of BDNF processing. To determine the cellular mechanism whereby gp120
    produces an accumulation of proBDNF, we examined the levels of intracellular
    and extracellular enzymes that proteolytically cleave proBDNF furin
    and tissue plasminogen, respectively. In rat neurons exposed to gp120,
    intracellular furin levels decreased before cell death, whereas tissue
    plasminogen changed only during apoptosis. Our data suggest that
    HIV, through gp120, reduces proBDNF processing by affecting furin
    levels, and therefore causes an altered balance between antiapoptotic
    and proapoptotic neurotrophins. Our studies identify a new mechanism
    that may explain how HIV promotes neuronal injury.
    BibTeX:
    @article{Bachis2012,
      author = {Bachis, Alessia and Avdoshina, Valeriya and Zecca, Luigi and Parsadanian, Maia and Mocchetti, Italo},
      title = {Human immunodeficiency virus type 1 alters brain-derived neurotrophic factor processing in neurons.},
      journal = {J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057 and CNR Institute of Biomedical Technologies, 20090 Segrate, Italy.},
      year = {2012},
      volume = {32},
      number = {28},
      pages = {9477--9484},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.0865-12.2012},
      doi = {http://doi.org/10.1523/JNEUROSCI.0865-12.2012}
    }
    
    Conant, K., Lim, S.T., Randall, B. & Maguire-Zeiss, K.A. Matrix Metalloproteinase Dependent Cleavage of Cell Adhesion Molecules in the Pathogenesis of CNS Dysfunction with HIV and Methamphetamine. 2012 Curr HIV ResSchool: Department of Neuroscience, Georgetown University Medical Center, Research Building EP-16, 3970 Reservoir Rd, Washington, DC 20007, USA. kec84@georgetown.edu.   
    Abstract: Physiologically appropriate levels of matrix metalloproteinases (MMPs)
    are likely important to varied aspects of CNS function. In particular,
    these enzymes may contribute to neuronal activity dependent synaptic
    plasticity and to cell mobility in processes including stem cell
    migration and immune surveillance. Levels of MMPs may, however, be
    substantially increased in the setting of HIV infection with methamphetamine
    abuse. Elevated MMP levels might in turn influence integrity of the
    blood brain barrier, as has been demonstrated in published work.
    Herein we suggest that elevated levels of MMPs can also contribute
    to microglial activation as well as neuronal and synaptic injury
    through a mechanism that involves cleavage of specific cell and synaptic
    adhesion molecules.
    BibTeX:
    @article{Conant2012,
      author = {Conant, Katherine and Lim, Seung T. and Randall, Brad and Maguire-Zeiss, Kathleen A.},
      title = {Matrix Metalloproteinase Dependent Cleavage of Cell Adhesion Molecules in the Pathogenesis of CNS Dysfunction with HIV and Methamphetamine.},
      journal = {Curr HIV Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building EP-16, 3970 Reservoir Rd, Washington, DC 20007, USA. kec84@georgetown.edu.},
      year = {2012}
    }
    
    Desforges, N.M., Hebron, M.L., Algarzae, N.K., Lonskaya, I. & Moussa, C.E.-H. Fractalkine Mediates Communication between Pathogenic Proteins and Microglia: Implications of Anti-Inflammatory Treatments in Different Stages of Neurodegenerative Diseases. 2012 Int J Alzheimers Dis
    Vol. 2012, pp. 345472School: town University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: The role of inflammation in neurodegenerative diseases has been widely
    demonstrated. Intraneuronal protein accumulation may regulate microglial
    activity via the fractalkine (CX3CL1) signaling pathway that provides
    a mechanism through which neurons communicate with microglia. CX3CL1
    levels fluctuate in different stages of neurodegenerative diseases
    and in various animal models, warranting further investigation of
    the mechanisms underlying microglial response to pathogenic proteins,
    including Tau, ?-amyloid (AΒ), and α-synuclein. The temporal relationship
    between microglial activity and localization of pathogenic proteins
    (intra- versus extracellular) likely determines whether neuroinflammation
    mitigates or exacerbates disease progression. Evidence in transgenic
    models suggests a beneficial effect of microglial activity on clearance
    of proteins like AΒ and a detrimental effect on Tau modification,
    but the role of CX3CL1 signaling in α-synucleinopathies is less clear.
    Here we review the nature of fractalkine-mediated neuronmicroglia
    interaction, which has significant implications for the efficacy
    of anti-inflammatory treatments during different stages of neurodegenerative
    pathology. Specifically, it is likely that anti-inflammatory treatment
    in early stages of disease during intraneuronal accumulation of proteins
    could be beneficial, while anti-inflammatory treatment in later stages
    when proteins are secreted to the extracellular space could exacerbate
    disease progression.
    BibTeX:
    @article{Desforges2012,
      author = {Desforges, Nicole M. and Hebron, Michaeline L. and Algarzae, Norah K. and Lonskaya, Irina and Moussa, Charbel E-H.},
      title = {Fractalkine Mediates Communication between Pathogenic Proteins and Microglia: Implications of Anti-Inflammatory Treatments in Different Stages of Neurodegenerative Diseases.},
      journal = {Int J Alzheimers Dis},
      school = {town University Medical Center, Washington, DC 20057, USA.},
      year = {2012},
      volume = {2012},
      pages = {345472},
      url = {http://dx.doi.org/10.1155/2012/345472},
      doi = {http://doi.org/10.1155/2012/345472}
    }
    
    DeWitt, I. & Rauschecker, J.P. Phoneme and word recognition in the auditory ventral stream. 2012 Proc Natl Acad Sci U S A
    Vol. 109(8), pp. E505-E514School: Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. id32@georgetown.edu 
    DOI URL 
    Abstract: Spoken word recognition requires complex, invariant representations.
    Using a meta-analytic approach incorporating more than 100 functional
    imaging experiments, we show that preference for complex sounds emerges
    in the human auditory ventral stream in a hierarchical fashion, consistent
    with nonhuman primate electrophysiology. Examining speech sounds,
    we show that activation associated with the processing of short-timescale
    patterns (i.e., phonemes) is consistently localized to left mid-superior
    temporal gyrus (STG), whereas activation associated with the integration
    of phonemes into temporally complex patterns (i.e., words) is consistently
    localized to left anterior STG. Further, we show left mid- to anterior
    STG is reliably implicated in the invariant representation of phonetic
    forms and that this area also responds preferentially to phonetic
    sounds, above artificial control sounds or environmental sounds.
    Together, this shows increasing encoding specificity and invariance
    along the auditory ventral stream for temporally complex speech sounds.
    BibTeX:
    @article{DeWitt2012,
      author = {DeWitt, Iain and Rauschecker, Josef P.},
      title = {Phoneme and word recognition in the auditory ventral stream.},
      journal = {Proc Natl Acad Sci U S A},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. id32@georgetown.edu},
      year = {2012},
      volume = {109},
      number = {8},
      pages = {E505--E514},
      url = {http://dx.doi.org/10.1073/pnas.1113427109},
      doi = {http://doi.org/10.1073/pnas.1113427109}
    }
    
    Dumanis, S.B., Chamberlain, K.A., Jin Sohn, Y., Jin Lee, Y., Guénette, S.Y., Suzuki, T., Mathews, P.M., Pak, D.T., Rebeck, G.W., Suh, Y.-H., Park, H.-S. & Hoe, H.-S. FE65 as a link between VLDLR and APP to regulate their trafficking and processing. 2012 Mol Neurodegener
    Vol. 7, pp. 9School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA. hh69@georgetown.edu. 
    DOI URL 
    Abstract: ABSTRACT:Several studies found that FE65, a cytoplasmic adaptor protein,
    interacts with APP and LRP1, altering the trafficking and processing
    of APP. We have previously shown that FE65 interacts with the ApoE
    receptor, ApoER2, altering its trafficking and processing. Interestingly,
    it has been shown that FE65 can act as a linker between APP and LRP1
    or ApoER2. In the present study, we tested whether FE65 can interact
    with another ApoE receptor, VLDLR, thereby altering its trafficking
    and processing, and whether FE65 can serve as a linker between APP
    and VLDLR.We found that FE65 interacted with VLDLR using GST pull-down
    and co-immunoprecipitation assays in COS7 cells and in brain lysates.
    This interaction occurs via the PTB1 domain of FE65. Co-transfection
    with FE65 and full length VLDLR increased secreted VLDLR (sVLDLR);
    however, the levels of VLDLR C-terminal fragment (CTF) were undetectable
    as a result of proteasomal degradation. Additionally, FE65 increased
    cell surface levels of VLDLR. Moreover, we identified a novel complex
    between VLDLR and APP, which altered trafficking and processing of
    both proteins. Furthermore, immunoprecipitation results demonstrated
    that the presence of FE65 increased the interaction between APP and
    VLDLR in vitro and in vivo.These data suggest that FE65 can regulate
    VLDLR trafficking and processing. Additionally, the interaction between
    VLDLR and APP altered both protein's trafficking and processing.
    Finally, our data suggest that FE65 serves as a link between VLDLR
    and APP. This novel interaction adds to a growing body of literature
    indicating trimeric complexes with various ApoE Receptors and APP.
    BibTeX:
    @article{Dumanis2012a,
      author = {Dumanis, Sonya B. and Chamberlain, Kelly A. and Jin Sohn, Yoo and Jin Lee, Young and Guénette, Suzanne Y. and Suzuki, Toshiharu and Mathews, Paul M. and Pak, Daniel Ts and Rebeck, G William and Suh, Yoo-Hun and Park, Hee-Sae and Hoe, Hyang-Sook},
      title = {FE65 as a link between VLDLR and APP to regulate their trafficking and processing.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA. hh69@georgetown.edu.},
      year = {2012},
      volume = {7},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1750-1326-7-9},
      doi = {http://doi.org/10.1186/1750-1326-7-9}
    }
    
    Dumanis, S.B., Dibattista, A.M., Miessau, M., Moussa, C.E.H. & William Rebeck, G. APOE genotype affects the presynaptic compartment of glutamatergic nerve terminals. 2012 J NeurochemSchool: Department of Neuroscience, Georgetown University Medical Center.  DOI URL 
    Abstract: Apolipoprotein E (APOE) genotype affects outcomes of Alzheimer's Disease
    and other conditions of brain damage. Using APOE knock-in mice, we
    have previously shown that APOE-?4 Targeted Replacement (TR) mice
    have fewer dendritic spines and reduced branching in cortical neurons.
    Since dendritic spines are postsynaptic sites of excitatory neurotransmission,
    we used APOE TR mice to examine whether APOE genotype affected the
    various elements of the glutamate-glutamine cycle. We found that
    levels of glutamine synthetase and glutamate uptake transporters
    were unchanged among the APOE genotypes. However, compared to APOE-?3
    TR mice, APOE-?4 TR mice had decreased glutaminase levels (18
    p<0.05), suggesting decreased conversion of glutamine to glutamate.
    APOE-?4 TR mice also had increased levels of the vesicular glutamate
    transporter VGLUT1 (20 p<0.05), suggesting that APOE genotype
    affects presynaptic terminal composition. To address whether these
    changes affected normal neurotransmission, we examined the production
    and metabolism of glutamate and glutamine at 4-5 months and 1 year.
    Using high frequency (13) C / (1) H nuclear magnetic resonance (NMR)
    spectroscopy, we found that APOE-?4 TR mice have decreased production
    of glutamate and increased levels of glutamine. These factors may
    contribute to the increased risk of neurodegeneration associated
    with APOE-?4, and also act as surrogate markers for AD risk. © 2012
    The Authors Journal of Neurochemistry © 2012 International Society
    for Neurochemistry.
    BibTeX:
    @article{Dumanis2012,
      author = {Dumanis, Sonya B. and Dibattista, Amanda M. and Miessau, Matthew and Moussa, Charbel E H. and William Rebeck, G.},
      title = {APOE genotype affects the presynaptic compartment of glutamatergic nerve terminals.},
      journal = {J Neurochem},
      school = {Department of Neuroscience, Georgetown University Medical Center.},
      year = {2012},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2012.07908.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2012.07908.x}
    }
    
    Forcelli, P.A., Janssen, M.J., Vicini, S. & Gale, K. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. 2012 Ann NeurolSchool: Interdisciplinary Program in Neuroscience and Physiology, Georgetown University, School of Medicine, Washington, DC; Department of Pharmacology and Physiology, Georgetown University, School of Medicine, Washington, DC. Paf22@georgetown.edu.  DOI URL 
    Abstract: OBJECTIVE: Drug exposure during critical periods of brain development
    may adversely affect nervous system function, posing a challenge
    for treating infants. This is of particular concern for treating
    neonatal seizures, as early life exposure to drugs such as phenobarbital
    is associated with adverse neurological outcomes in patients and
    induction of neuronal apoptosis in animal models. The functional
    significance of the preclinical neurotoxicity has been questioned
    due to the absence of evidence for functional impairment associated
    with drug-induced developmental apoptosis. METHODS: We used patch-clamp
    recordings to examine functional synaptic maturation in striatal
    medium spiny neurons from neonatal rats exposed to antiepileptic
    drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine)
    and without proapoptotic action (levetiracetam). Phenobarbital-exposed
    rats were also assessed for reversal learning at weaning. RESULTS:
    Recordings from control animals revealed increased inhibitory and
    excitatory synaptic connectivity between postnatal day (P)10 and
    P18. This maturation was absent in rats exposed at P7 to a single
    dose of phenobarbital, phenytoin, or lamotrigine. Additionally, phenobarbital
    exposure impaired striatal-mediated behavior on P25. Neuroprotective
    pretreatment with melatonin, which prevents drug-induced neurodevelopmental
    apoptosis, prevented the drug-induced disruption in maturation. Levetiracetam
    was found not to disrupt synaptic development. INTERPRETATION: Our
    results provide the first evidence that exposure to antiepileptic
    drugs during a sensitive postnatal period impairs physiological maturation
    of synapses in neurons that survive the initial drug insult. These
    findings suggest a mechanism by which early life exposure to antiepileptic
    drugs can impact cognitive and behavioral outcomes, underscoring
    the need to identify therapies that control seizures without compromising
    synaptic maturation. ANN NEUROL 2012;
    BibTeX:
    @article{Forcelli2012,
      author = {Forcelli, Patrick A. and Janssen, Megan J. and Vicini, Stefano and Gale, Karen},
      title = {Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development.},
      journal = {Ann Neurol},
      school = {Interdisciplinary Program in Neuroscience and Physiology, Georgetown University, School of Medicine, Washington, DC; Department of Pharmacology and Physiology, Georgetown University, School of Medicine, Washington, DC. Paf22@georgetown.edu.},
      year = {2012},
      url = {http://dx.doi.org/10.1002/ana.23600},
      doi = {http://doi.org/10.1002/ana.23600}
    }
    
    Gonzalez-Sulser, A., Wang, J., Queenan, B.N., Avoli, M., Vicini, S. & Dzakpasu, R. Hippocampal neuron firing and local field potentials in the in vitro 4-aminopyridine epilepsy model. 2012 J Neurophysiol
    Vol. 108(9), pp. 2568-2580School: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia 20007, USA. aag46@georgetown.edu 
    DOI URL 
    Abstract: Excessive synchronous neuronal activity is a defining feature of epileptic
    activity. We previously characterized the properties of distinct
    glutamatergic and GABAergic transmission-dependent synchronous epileptiform
    discharges in mouse hippocampal slices using the 4-aminopyridine
    model of epilepsy. In the present study, we sought to identify the
    specific hippocampal neuronal populations that initiate and underlie
    these local field potentials (LFPs). A perforated multielectrode
    array was used to simultaneously record multiunit action potential
    firing and LFPs during spontaneous epileptiform activity. LFPs had
    distinct components based on the initiation site, extent of propagation,
    and pharmacological sensitivity. Individual units, located in different
    hippocampal subregions, fired action potentials during these LFPs.
    A specific neuron subgroup generated sustained action potential firing
    throughout the various components of the LFPs. The activity of this
    subgroup preceded the LFPs observed in the presence of antagonists
    of ionotropic glutamatergic synaptic transmission. In the absence
    of ionotropic glutamatergic and GABAergic transmission, LFPs disappeared,
    but units with shorter spike duration and high basal firing rates
    were still active. These spontaneously active units had an increased
    level of activity during LFPs and consistently preceded all LFPs
    recorded before blockade of synaptic transmission. Our findings reveal
    that neuronal subpopulations with interneuron properties are likely
    responsible for initiating synchronous activity in an in vitro model
    of epileptiform discharges.
    BibTeX:
    @article{Gonzalez-Sulser2012,
      author = {Gonzalez-Sulser, Alfredo and Wang, Jing and Queenan, Bridget N. and Avoli, Massimo and Vicini, Stefano and Dzakpasu, Rhonda},
      title = {Hippocampal neuron firing and local field potentials in the in vitro 4-aminopyridine epilepsy model.},
      journal = {J Neurophysiol},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia 20007, USA. aag46@georgetown.edu},
      year = {2012},
      volume = {108},
      number = {9},
      pages = {2568--2580},
      url = {http://dx.doi.org/10.1152/jn.00363.2012},
      doi = {http://doi.org/10.1152/jn.00363.2012}
    }
    
    Gordon, E.M., Breeden, A.L., Bean, S.E. & Vaidya, C.J. Working memory-related changes in functional connectivity persist beyond task disengagement. 2012 Hum Brain MappSchool: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC. emg56@georgetown.edu.  DOI URL 
    Abstract: We examined whether altered connectivity in functional networks during
    working memory performance persists following conclusion of that
    performance, into a subsequent resting state. We conducted functional
    magnetic resonance imaging (fMRI) in 50 young adults during an initial
    resting state, followed by an N-back working memory task and a subsequent
    resting state, in order to examine changes in functional connectivity
    within and between the default-mode network (DMN) and the task-positive
    network (TPN) across the three states. We found that alterations
    in connectivity observed during the N-back task persisted into the
    subsequent resting state within the TPN and between the DMN and TPN,
    but not within the DMN. Further, both speed of working memory performance
    and TPN connectivity strength during the N-back task predicted connectivity
    strength in the subsequent resting state. Finally, DMN connectivity
    measured before and during the N-back task predicted individual differences
    in self-reported inattentiveness, but this association was not found
    during the post-task resting state. Together, these findings have
    important implications for models of how the brain recovers following
    effortful cognition, as well as for experimental designs using resting
    and task scans. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    BibTeX:
    @article{Gordon2012b,
      author = {Gordon, Evan M. and Breeden, Andrew L. and Bean, Stephanie E. and Vaidya, Chandan J.},
      title = {Working memory-related changes in functional connectivity persist beyond task disengagement.},
      journal = {Hum Brain Mapp},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC. emg56@georgetown.edu.},
      year = {2012},
      url = {http://dx.doi.org/10.1002/hbm.22230},
      doi = {http://doi.org/10.1002/hbm.22230}
    }
    
    Gordon, E.M., Stollstorff, M., Devaney, J.M., Bean, S. & Vaidya, C.J. Effect of dopamine transporter genotype on intrinsic functional connectivity depends on cognitive state. 2012 Cereb Cortex
    Vol. 22(9), pp. 2182-2196School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Functional connectivity between brain regions can define large-scale
    neural networks and provide information about relationships between
    those networks. We examined how relationships within and across intrinsic
    connectivity networks were 1) sensitive to individual differences
    in dopaminergic function, 2) modulated by cognitive state, and 3)
    associated with executive behavioral traits. We found that regardless
    of cognitive state, connections between frontal, parietal, and striatal
    nodes of Task-Positive networks (TPNs) and Task-Negative networks
    (TNNs) showed higher functional connectivity in 10/10 homozygotes
    of the dopamine transporter gene, a polymorphism influencing synaptic
    dopamine, than in 9/10 heterozygotes. However, performance of a working
    memory task (a state requiring dopamine release) modulated genotype
    differences selectively, such that cross-network connectivity between
    TPNs and TNNs was higher in 10/10 than 9/10 subjects during working
    memory but not during rest. This increased cross-network connectivity
    was associated with increased self-reported measures of impulsivity
    and inattention traits. By linking a gene regulating synaptic dopamine
    to a phenotype characterized by inefficient executive function, these
    findings validate cross-network connectivity as an endophenotype
    of executive dysfunction.
    BibTeX:
    @article{Gordon2012,
      author = {Gordon, Evan M. and Stollstorff, Melanie and Devaney, Joseph M. and Bean, Stephanie and Vaidya, Chandan J.},
      title = {Effect of dopamine transporter genotype on intrinsic functional connectivity depends on cognitive state.},
      journal = {Cereb Cortex},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2012},
      volume = {22},
      number = {9},
      pages = {2182--2196},
      url = {http://dx.doi.org/10.1093/cercor/bhr305},
      doi = {http://doi.org/10.1093/cercor/bhr305}
    }
    
    Gordon, E.M., Stollstorff, M. & Vaidya, C.J. Using spatial multiple regression to identify intrinsic connectivity networks involved in working memory performance. 2012 Hum Brain Mapp
    Vol. 33(7), pp. 1536-1552School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA. emg56@georgetown.edu 
    DOI URL 
    Abstract: Many researchers have noted that the functional architecture of the
    human brain is relatively invariant during task performance and the
    resting state. Indeed, intrinsic connectivity networks (ICNs) revealed
    by resting-state functional connectivity analyses are spatially similar
    to regions activated during cognitive tasks. This suggests that patterns
    of task-related activation in individual subjects may result from
    the engagement of one or more of these ICNs; however, this has not
    been tested. We used a novel analysis, spatial multiple regression,
    to test whether the patterns of activation during an N-back working
    memory task could be well described by a linear combination of ICNs
    delineated using Independent Components Analysis at rest. We found
    that across subjects, the cingulo-opercular Set Maintenance ICN,
    as well as right and left Frontoparietal Control ICNs, were reliably
    activated during working memory, while Default Mode and Visual ICNs
    were reliably deactivated. Further, involvement of Set Maintenance,
    Frontoparietal Control, and Dorsal Attention ICNs was sensitive to
    varying working memory load. Finally, the degree of left Frontoparietal
    Control network activation predicted response speed, while activation
    in both left Frontoparietal Control and Dorsal Attention networks
    predicted task accuracy. These results suggest that a close relationship
    between resting-state networks and task-evoked activation is functionally
    relevant for behavior, and that spatial multiple regression analysis
    is a suitable method for revealing that relationship.
    BibTeX:
    @article{Gordon2012a,
      author = {Gordon, Evan M. and Stollstorff, Melanie and Vaidya, Chandan J.},
      title = {Using spatial multiple regression to identify intrinsic connectivity networks involved in working memory performance.},
      journal = {Hum Brain Mapp},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA. emg56@georgetown.edu},
      year = {2012},
      volume = {33},
      number = {7},
      pages = {1536--1552},
      url = {http://dx.doi.org/10.1002/hbm.21306},
      doi = {http://doi.org/10.1002/hbm.21306}
    }
    
    Harris-Love, M. Transcranial magnetic stimulation for the prediction and enhancement of rehabilitation treatment effects. 2012 J Neurol Phys Ther
    Vol. 36(2), pp. 87-93School: Interdisciplinary Program in Neuroscience, Medstar National Rehabilitation Hospital, Georgetown University, Washington, District of Columbia. 
    DOI URL 
    Abstract: In this update on rehabilitation technology, transcranial magnetic
    stimulation (TMS), a technique that allows noninvasive stimulation
    of the brain, is examined. The background and basic principles of
    TMS are reviewed, and its usefulness as a tool to inform and possibly
    augment the rehabilitation process is discussed. The three main paradigms
    by which TMS is applied-physiological measurement, disruption/virtual
    lesion studies, and modulation of cortical excitability-are discussed
    relative to the types of scientific information each paradigm can
    provide and their potential clinical usefulness in the future. One
    of the more exciting prospects is that, when combined with rehabilitation
    training, TMS modulation of cortical excitability could potentially
    enhance the effects of rehabilitation and lead to greater levels
    of recovery than are currently attainable with rehabilitation alone.
    It is concluded that current studies must focus on the mechanisms
    of recovery based on the specific structures and processes affected
    by the disorder and the neural effects of specific rehabilitation
    interventions in order for the potential of TMS-augmented rehabilitation
    to be realized.
    BibTeX:
    @article{Harris-Love2012,
      author = {Harris-Love, Michelle},
      title = {Transcranial magnetic stimulation for the prediction and enhancement of rehabilitation treatment effects.},
      journal = {J Neurol Phys Ther},
      school = { Interdisciplinary Program in Neuroscience, Medstar National Rehabilitation Hospital, Georgetown University, Washington, District of Columbia.},
      year = {2012},
      volume = {36},
      number = {2},
      pages = {87--93},
      url = {http://dx.doi.org/10.1097/NPT.0b013e3182564d26},
      doi = {http://doi.org/10.1097/NPT.0b013e3182564d26}
    }
    
    Herman, A.M., Khandelwal, P.J., Rebeck, G.W. & Moussa, C.E.-H. Wild type TDP-43 induces neuro-inflammation and alters APP metabolism in lentiviral gene transfer models. 2012 Exp Neurol
    Vol. 235(1), pp. 297-305School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: The transactivation DNA-binding protein (TDP-43) pathology is associated
    with fronto-temporal lobar dementia (FTLD) with ubiquitinated inclusions
    and some cases of Alzheimer's disease (AD). Proteolytic fragments
    of ?-amyloid precursor protein (?APP) are detected in AD as well
    as the cerebrospinal fluid (CSF) from FTLD and Amyotrophic Lateral
    Sclerosis (ALS) patients, suggesting alteration in APP processing.
    Because of the overlap in TDP-43 pathology between FTLD and AD, we
    sought to determine whether there is a relationship between TDP-43
    and APP metabolism. We generated gene transfer models using lentiviral
    delivery of human TDP-43 and AΒ(1-42) into the rat primary motor
    cortex and examined their role 2 weeks post-injection. Expression
    of TDP-43 and/or AΒ(1-42) increase pro-inflammatory markers, including
    Interleukin (IL)-6, tumor necrosis factor (TNF-?), glial neurofibrillary
    proteins (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1).
    Lentiviral AΒ(1-42) up-regulates endogenous TDP-43 and promotes its
    phosphorylation, aggregation and cleavage into 35 kDa fragments.
    Inversely, lentiviral TDP-43 expression increases the levels and
    activity of ?-secretase (BACE), accelerating production of APP C-terminal
    fragments (C99) and AΒ(1-40). Here we show that TDP-43 up-regulates
    APP metabolism and suggest a mechanistic link between TDP-43 and
    BACE.
    BibTeX:
    @article{Herman2012a,
      author = {Herman, Alexander M. and Khandelwal, Preeti J. and Rebeck, G William and Moussa, Charbel E-H.},
      title = {Wild type TDP-43 induces neuro-inflammation and alters APP metabolism in lentiviral gene transfer models.},
      journal = {Exp Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2012},
      volume = {235},
      number = {1},
      pages = {297--305},
      url = {http://dx.doi.org/10.1016/j.expneurol.2012.02.011},
      doi = {http://doi.org/10.1016/j.expneurol.2012.02.011}
    }
    
    Herman, M.A., Gillis, R.A., Vicini, S., Dretchen, K.L. & Sahibzada, N. Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of ?-opioid receptors. 2012 J Neurophysiol
    Vol. 107(3), pp. 1022-1031School: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: Our laboratory previously reported that gastric activity is controlled
    by a robust GABA(A) receptor-mediated inhibition in the medial nucleus
    of the tractus solitarius (mNTS) (Herman et al. 2009), and that ?-opioid
    receptor activation inhibits gastric tone by suppression of this
    GABA signaling (Herman et al. 2010). These data raised two questions:
    1) whether any of this inhibition was due to tonic GABA(A) receptor-mediated
    conductance in the mNTS; and 2) whether ?-opioid receptor activation
    suppressed both tonic and phasic GABA signaling. In whole cell recordings
    from rat mNTS neurons, application of three GABA(A) receptor antagonists
    (gabazine, bicuculline, and picrotoxin) produced a persistent reduction
    in holding current and decrease in population variance or root mean
    square (RMS) noise, suggesting a blockade of tonic GABA signaling.
    Application of gabazine at a lower concentration abolished phasic
    currents, but had no effect on tonic currents or RMS noise. Application
    of the ?-subunit preferring agonist gaboxadol (THIP) produced a dose-dependent
    persistent increase in holding current and RMS noise. Pretreatment
    with tetrodotoxin prevented the action of gabazine, but had no effect
    on the THIP-induced current. Membrane excitability was unaffected
    by the selective blockade of phasic inhibition, but was increased
    by blockade of both phasic and tonic currents. In contrast, activation
    of tonic currents decreased membrane excitability. Application of
    the ?-opioid receptor agonist DAMGO produced a persistent reduction
    in holding current that was not observed following pretreatment with
    a GABA(A) receptor antagonist and was not evident in mice lacking
    the ?-subunit. These data suggest that mNTS neurons possess a robust
    tonic inhibition that is mediated by GABA(A) receptors containing
    the ?-subunit, that determines membrane excitability, and that is
    partially regulated by ?-opioid receptors.
    BibTeX:
    @article{Herman2012,
      author = {Herman, Melissa A. and Gillis, Richard A. and Vicini, Stefano and Dretchen, Kenneth L. and Sahibzada, Niaz},
      title = {Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of ?-opioid receptors.},
      journal = {J Neurophysiol},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA.},
      year = {2012},
      volume = {107},
      number = {3},
      pages = {1022--1031},
      url = {http://dx.doi.org/10.1152/jn.00853.2011},
      doi = {http://doi.org/10.1152/jn.00853.2011}
    }
    
    Hoe, H.-S., Lee, H.-K. & Pak, D.T.S. The upside of APP at synapses. 2012 CNS Neurosci Ther
    Vol. 18(1), pp. 47-56School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. hh69@georgetown.edu 
    DOI URL 
    Abstract: The memory dysfunctions that characterize Alzheimer's disease (AD)
    are strongly correlated with synapse loss. The amyloid precursor
    protein (APP) and its cleavage product AΒ play central roles in synapse
    and memory loss, and thus are strongly implicated in the pathogenesis
    of AD. Numerous in vitro and transgenic AD mouse model studies have
    shown that overexpression of APP leads to AΒ accumulation, which
    causes decreased synaptic activity and dendritic spine density. However,
    the normal synaptic function of APP itself is not fully understood.
    Several recent studies have found that full-length APP promotes synaptic
    activity, synapse formation, and dendritic spine formation. These
    findings cast APP as a potential key player in learning and memory.
    It is of interest that the synaptic functions of full-length APP
    are opposite to the effects associated with pathological AΒ accumulation.
    In this review, we will summarize the normal functions of APP at
    synapses and spines along with other known functions of APP, including
    its role in cell motility, neuronal migration, and neurite outgrowth.
    These studies shed light on the physiological actions of APP, independent
    of AΒ effects, and thus lead to a better understanding of the synaptic
    dysfunctions associated with AD.
    BibTeX:
    @article{Hoe2012,
      author = {Hoe, Hyang-Sook and Lee, Hey-Kyoung and Pak, Daniel T S.},
      title = {The upside of APP at synapses.},
      journal = {CNS Neurosci Ther},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. hh69@georgetown.edu},
      year = {2012},
      volume = {18},
      number = {1},
      pages = {47--56},
      url = {http://dx.doi.org/10.1111/j.1755-5949.2010.00221.x},
      doi = {http://doi.org/10.1111/j.1755-5949.2010.00221.x}
    }
    
    Khandelwal, P.J., Dumanis, S.B., Herman, A.M., Rebeck, G.W. & Moussa, C.E.-H. Wild type and P301L mutant Tau promote neuro-inflammation and α-synuclein accumulation in lentiviral gene delivery models. 2012 Mol Cell Neurosci
    Vol. 49(1), pp. 44-53School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Neurodegeneration involves multiple pathogenic proteins, including
    Tau, AΒ, TDP-43 and α-synuclein, but there is little information
    how these pathogenic proteins interact. We cloned human wild type
    4 repeat Tau (Tau(wt)) and mutant Tau(P301L) into a lentivirus and
    performed stereotaxic injection into the rat motor cortex to examine
    Tau modification, neuro-inflammation and changes of other proteins
    associated with neurodegeneration. Tau(P301L) was associated with
    more phosphorylation of Tau, including Thr 181 and Ser 262 residues
    and resulted in more aggregation. Both forms of Tau expression increased
    glycogen synthase kinase-3 (GSK-3) activity, polo-like kinase-2 (PLK2)
    levels and decreased protein phosphatase activity, but had no effects
    on casein kinase-1 (CK1). No changes were observed in glial fibrillary
    acidic protein (GFAP) staining with either Tau(wt) or Tau(P301L),
    but both caused microglial changes and higher interleukin-6 (IL-6)
    and tumor necrosis factor-? (TNF-?) levels. Tau(wt) and Tau(P301L)
    increased the levels of endogenous α-synuclein, but not ?-amyloid
    precursor protein (?APP) or Tar-DNA binding protein (TDP-43). The
    levels of phosphorylated Ser-129 α-synuclein (p-Ser129) were also
    increased with Tau(wt) and Tau(P301L) expressing animals. These data
    suggest that Tau(wt) and Tau(P301L) alter kinase activities, but
    they differentially induce inflammation, Tau modification and α-synuclein
    phosphorylation. This change of α-synuclein in Tau gene transfer
    models suggests that Tau pathology may lead to α-synuclein modification
    in neurodegenerative diseases.
    BibTeX:
    @article{Khandelwal2012,
      author = {Khandelwal, Preeti J. and Dumanis, Sonya B. and Herman, Alexander M. and Rebeck, G William and Moussa, Charbel E-H.},
      title = {Wild type and P301L mutant Tau promote neuro-inflammation and α-synuclein accumulation in lentiviral gene delivery models.},
      journal = {Mol Cell Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2012},
      volume = {49},
      number = {1},
      pages = {44--53},
      url = {http://dx.doi.org/10.1016/j.mcn.2011.09.002},
      doi = {http://doi.org/10.1016/j.mcn.2011.09.002}
    }
    
    Ku?mierek, P., Ortiz, M. & Rauschecker, J.P. Sound-identity processing in early areas of the auditory ventral stream in the macaque. 2012 J Neurophysiol
    Vol. 107(4), pp. 1123-1141School: sity Medical Center, Washington, District of Columbia 20057, USA. pk83@georgetown.edu 
    DOI URL 
    Abstract: Auditory cortical processing is thought to be accomplished along two
    processing streams. The existence of a posterior/dorsal stream dealing,
    among others, with the processing of spatial aspects of sound has
    been corroborated by numerous studies in several species. An anterior/ventral
    stream for the processing of nonspatial sound qualities, including
    the identification of sounds such as species-specific vocalizations,
    has also received much support. Originally discovered in anterolateral
    belt cortex, most recent work on the anterior/ventral pathway has
    been performed on far anterior superior temporal (ST) areas and on
    ventrolateral prefrontal cortex (VLPFC). Regions of the anterior/ventral
    stream near its origin in early auditory areas have been less explored.
    In the present study, we examined three early auditory regions with
    different anteroposterior locations (caudal, middle, and rostral)
    in awake rhesus macaques. We analyzed how well classification based
    on sound-evoked activity patterns of neuronal populations replicates
    the original stimulus categories. Of the three regions, the rostral
    region (rR), which included core area R and medial belt area RM,
    yielded the greatest classification success across all stimulus classes
    or between classes of natural sounds. Starting from ?80 ms past stimulus
    onset, clustering based on the population response in rR became clearly
    more successful than clustering based on responses from any other
    region. Our study demonstrates that specialization for sound-identity
    processing can be found very early in the auditory ventral stream.
    Furthermore, the fact that this processing develops over time can
    shed light on underlying mechanisms. Finally, we show that population
    analysis is a more sensitive method for revealing functional specialization
    than conventional types of analysis.
    BibTeX:
    @article{Kusmierek2012,
      author = {Ku?mierek, Pawe? and Ortiz, Michael and Rauschecker, Josef P.},
      title = {Sound-identity processing in early areas of the auditory ventral stream in the macaque.},
      journal = {J Neurophysiol},
      school = {sity Medical Center, Washington, District of Columbia 20057, USA. pk83@georgetown.edu},
      year = {2012},
      volume = {107},
      number = {4},
      pages = {1123--1141},
      url = {http://dx.doi.org/10.1152/jn.00793.2011},
      doi = {http://doi.org/10.1152/jn.00793.2011}
    }
    
    Leaver, A.M., Seydell-Greenwald, A., Turesky, T.K., Morgan, S., Kim, H.J. & Rauschecker, J.P. Cortico-limbic morphology separates tinnitus from tinnitus distress. 2012 Front Syst Neurosci
    Vol. 6, pp. 21School: Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA. 
    DOI URL 
    Abstract: Tinnitus is a common auditory disorder characterized by a chronic
    ringing or buzzing "in the ear."Despite the auditory-perceptual nature
    of this disorder, a growing number of studies have reported neuroanatomical
    differences in tinnitus patients outside the auditory-perceptual
    system. Some have used this evidence to characterize chronic tinnitus
    as dysregulation of the auditory system, either resulting from inefficient
    inhibitory control or through the formation of aversive associations
    with tinnitus. It remains unclear, however, whether these "non-auditory"
    anatomical markers of tinnitus are related to the tinnitus signal
    itself, or merely to negative emotional reactions to tinnitus (i.e.,
    tinnitus distress). In the current study, we used anatomical MRI
    to identify neural markers of tinnitus, and measured their relationship
    to a variety of tinnitus characteristics and other factors often
    linked to tinnitus, such as hearing loss, depression, anxiety, and
    noise sensitivity. In a new cohort of participants, we confirmed
    that people with chronic tinnitus exhibit reduced gray matter in
    ventromedial prefrontal cortex (vmPFC) compared to controls matched
    for age and hearing loss. This effect was driven by reduced cortical
    surface area, and was not related to tinnitus distress, symptoms
    of depression or anxiety, noise sensitivity, or other factors. Instead,
    tinnitus distress was positively correlated with cortical thickness
    in the anterior insula in tinnitus patients, while symptoms of anxiety
    and depression were negatively correlated with cortical thickness
    in subcallosal anterior cingulate cortex (scACC) across all groups.
    Tinnitus patients also exhibited increased gyrification of dorsomedial
    prefrontal cortex (dmPFC), which was more severe in those patients
    with constant (vs. intermittent) tinnitus awareness. Our data suggest
    that the neural systems associated with chronic tinnitus are different
    from those involved in aversive or distressed reactions to tinnitus.
    BibTeX:
    @article{Leaver2012,
      author = {Leaver, Amber M. and Seydell-Greenwald, Anna and Turesky, Ted K. and Morgan, Susan and Kim, Hung J. and Rauschecker, Josef P.},
      title = {Cortico-limbic morphology separates tinnitus from tinnitus distress.},
      journal = {Front Syst Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA.},
      year = {2012},
      volume = {6},
      pages = {21},
      url = {http://dx.doi.org/10.3389/fnsys.2012.00021},
      doi = {http://doi.org/10.3389/fnsys.2012.00021}
    }
    
    Lim, S.T., Chang, A., Giuliano, R.E. & Federoff, H.J. Ectodomain shedding of nectin-1 regulates the maintenance of dendritic spine density. 2012 J Neurochem
    Vol. 120(5), pp. 741-751School: Neuroscience Department, Georgetown University Medical Center, Washington, District of Columbia 20057, USA. 
    DOI URL 
    Abstract: Synaptic remodeling has been postulated as a mechanism underlying
    synaptic plasticity and cell adhesion molecules are thought to contribute
    to this process. We examined the role of nectin-1 ectodomain shedding
    on synaptogenesis in cultured rat hippocampal neurons. Nectins are
    Ca(2+) -independent immunoglobulin-like adhesion molecules, involved
    in cell-cell adherens junctions. Herein, we show that the processing
    of nectin-1 occurs by multiple endoproteolytic steps both in vivo
    and in vitro. We identified regions containing two distinct cleavage
    sites within the ectodomain of nectin-1. By alanine scanning mutagenesis,
    two point mutations that disrupt nectin-1 ectodomain cleavage events
    were identified. Expression of these mutants significantly alters
    the density of dendritic spines. These findings suggest that ectodomain
    shedding of nectin-1 regulates dendritic spine density and related
    synaptic functions.
    BibTeX:
    @article{Lim2012,
      author = {Lim, Seung T. and Chang, Allison and Giuliano, Rita E. and Federoff, Howard J.},
      title = {Ectodomain shedding of nectin-1 regulates the maintenance of dendritic spine density.},
      journal = {J Neurochem},
      school = {Neuroscience Department, Georgetown University Medical Center, Washington, District of Columbia 20057, USA.},
      year = {2012},
      volume = {120},
      number = {5},
      pages = {741--751},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07592.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2011.07592.x}
    }
    
    Lonskaya, I., Hebron, M.L., Algarzae, N.K., Desforges, N. & Moussa, C.E.-H. Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease. 2012 Neuroscience
    Vol. 232C, pp. 90School: Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Parkinson's disease (PD) is a motor disorder that involves death of
    dopaminergic neurons in the substantia nigra pars compacta. Parkin
    is an autosomal recessive gene that is mutated in early onset PD.
    We investigated the role of parkin and autophagic clearance in postmortem
    nigrostriatal tissues from 22 non-familial sporadic PD patients and
    15 control samples. Parkin was insoluble with altered cytosolic expression
    in the nigrostriatum of sporadic PD. Parkin insolubility was associated
    with lack of degradation of ubiquitinated proteins and accumulation
    of α-synuclein and parkin in autophagosomes, suggesting autophagic
    defects in PD. To test parkin's role in mediating autophagic clearance,
    we used lentiviral gene transfer to express human wild type or mutant
    parkin (T240R) with α-synuclein in the rat striatum. Lentiviral expression
    of α-synuclein led to accumulation of autophagic vacuoles, while
    co-expression of parkin with α-synuclein facilitated autophagic clearance.
    Subcellular fractionation showed accumulation of α-synuclein and
    tau hyper-phosphorylation (p-Tau) in autophagosomes in gene transfer
    models, similar to the effects observed in PD brains, but parkin
    expression led to protein deposition into lysosomes. However, parkin
    loss of function mutation did not affect autophagic clearance. Taken
    together, these data suggest that functional parkin regulates autophagosome
    clearance, while decreased parkin solubility may alter normal autophagy
    in sporadic PD.
    BibTeX:
    @article{Lonskaya2012,
      author = {Lonskaya, I. and Hebron, M. L. and Algarzae, N. K. and Desforges, N. and Moussa, C E-H.},
      title = {Decreased parkin solubility is associated with impairment of autophagy in the nigrostriatum of sporadic Parkinson's disease.},
      journal = {Neuroscience},
      school = {Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2012},
      volume = {232C},
      pages = {90},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2012.12.018},
      doi = {http://doi.org/10.1016/j.neuroscience.2012.12.018}
    }
    
    Mhyre, T.R., Boyd, J.T., Hamill, R.W. & Maguire-Zeiss, K.A. Parkinson's disease. 2012 Subcell Biochem
    Vol. 65, pp. 389-455School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW NRB WP-24A, 20057, Washington, DC, USA, trm36@georgetown.edu. 
    DOI URL 
    Abstract: Parkinson's disease (PD) is the most common age-related motoric neurodegenerative
    disease initially described in the 1800's by James Parkinson as the
    'Shaking Palsy'. Loss of the neurotransmitter dopamine was recognized
    as underlying the pathophysiology of the motor dysfunction; subsequently
    discovery of dopamine replacement therapies brought substantial symptomatic
    benefit to PD patients. However, these therapies do not fully treat
    the clinical syndrome nor do they alter the natural history of this
    disorder motivating clinicians and researchers to further investigate
    the clinical phenotype, pathophysiology/pathobiology and etiology
    of this devastating disease. Although the exact cause of sporadic
    PD remains enigmatic studies of familial and rare toxicant forms
    of this disorder have laid the foundation for genome wide explorations
    and environmental studies. The combination of methodical clinical
    evaluation, systematic pathological studies and detailed genetic
    analyses have revealed that PD is a multifaceted disorder with a
    wide-range of clinical symptoms and pathology that include regions
    outside the dopamine system. One common thread in PD is the presence
    of intracytoplasmic inclusions that contain the protein, α-synuclein.
    The presence of toxic aggregated forms of α-synuclein (e.g., amyloid
    structures) are purported to be a harbinger of subsequent pathology.
    In fact, PD is both a cerebral amyloid disease and the most common
    synucleinopathy, that is, diseases that display accumulations of
    α-synuclein. Here we present our current understanding of PD etiology,
    pathology, clinical symptoms and therapeutic approaches with an emphasis
    on misfolded α-synuclein.
    BibTeX:
    @article{Mhyre2012,
      author = {Mhyre, Timothy R. and Boyd, James T. and Hamill, Robert W. and Maguire-Zeiss, Kathleen A.},
      title = {Parkinson's disease.},
      journal = {Subcell Biochem},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW NRB WP-24A, 20057, Washington, DC, USA, trm36@georgetown.edu.},
      year = {2012},
      volume = {65},
      pages = {389--455},
      url = {http://dx.doi.org/10.1007/978-94-007-5416-4_16},
      doi = {http://doi.org/10.1007/978-94-007-5416-4_16}
    }
    
    Minami, S.S., Clifford, T.G., Hoe, H.-S., Matsuoka, Y. & Rebeck, G.W. Fyn knock-down increases AΒ, decreases phospho-tau, and worsens spatial learning in 3xTg-AD mice. 2012 Neurobiol Aging
    Vol. 33(4), pp. 825.e15-825.e24School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Fyn kinase phosphorylates tau and exacerbates amyloid beta (AΒ)-mediated
    synaptic dysfunction. However, Fyn also increases the nonpathological
    cleavage of amyloid precursor protein (APP), suggesting opposing
    roles for Fyn in the pathogenesis of Alzheimer's disease (AD). To
    determine the effect of Fyn on both AΒ and tau pathologies, we crossed
    homozygous Alzheimer's disease triple transgenic (3?Tg) mice harboring
    mutations in amyloid precursor protein, presenilin-1, and tau with
    wild-type or Fyn knockout mice to generate Fyn(+/+)3?Tg(+/-) or Fyn(+/-)3?Tg(+/-)
    mice. We found that Fyn(+/-)3?Tg(+/-) mice had increased soluble
    and intracellular AΒ, and these changes were accompanied by impaired
    performance on the Morris water maze at 18 months. Fyn(+/-)3?Tg(+/-)
    mice had decreased phosphorylated tau at 15-18 months (as did Fyn
    knockout mice), but Fyn(+/-)3?Tg(+/-) mice had increased phosphorylated
    tau by 24 months. In addition, we observed that Fyn(+/-)3?Tg(+/-)
    males were delayed in developing AΒ pathology compared with females,
    and displayed better spatial learning performance at 18 months. Overall,
    these findings suggest that loss of Fyn at early stages of disease
    increases soluble AΒ accumulation and worsens spatial learning in
    the absence of changes in tau phosphorylation.
    BibTeX:
    @article{Minami2012,
      author = {Minami, S Sakura and Clifford, Thomas G. and Hoe, Hyang-Sook and Matsuoka, Yasuji and Rebeck, G William},
      title = {Fyn knock-down increases AΒ, decreases phospho-tau, and worsens spatial learning in 3xTg-AD mice.},
      journal = {Neurobiol Aging},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA.},
      year = {2012},
      volume = {33},
      number = {4},
      pages = {825.e15--825.e24},
      url = {http://dx.doi.org/10.1016/j.neurobiolaging.2011.05.014},
      doi = {http://doi.org/10.1016/j.neurobiolaging.2011.05.014}
    }
    
    Mocchetti, I., Bachis, A. & Avdoshina, V. Neurotoxicity of human immunodeficiency virus-1: viral proteins and axonal transport. 2012 Neurotox Res
    Vol. 21(1), pp. 79-89School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, New Research Building WP13, Washington, DC 20057, USA. moccheti@georgetown.edu 
    DOI URL 
    Abstract: Human immunodeficiency virus-1 (HIV) infection of the central nervous
    system may cause a neurological syndrome termed HIV-associated neurocognitive
    disorder (HAND) which includes minor neurocognitive disorders or
    a more severe form of motor and cognitive impairments. Although treatment
    with highly active antiretroviral agents decreases the load of HIV
    in the brain, the prevalence of mild forms of HAND is actually increased
    due to longer life. Therefore, adjunctive and combined therapies
    must be developed to prevent and perhaps reverse the neurologic deficits
    observed in individuals with HAND. Key to developing effective therapies
    is a better understanding of the molecular and cellular mechanisms
    by which the virus causes this disorder. A number of HIV proteins
    has been shown to be released from HIV-infected cells. Moreover,
    these proteins have been shown to possess neurotoxic properties.
    This review describes new evidence of a direct interaction of the
    HIV protein gp120 with neurons, which might play a role in the etiopathology
    of HAND.
    BibTeX:
    @article{Mocchetti2012a,
      author = {Mocchetti, Italo and Bachis, Alessia and Avdoshina, Valeriya},
      title = {Neurotoxicity of human immunodeficiency virus-1: viral proteins and axonal transport.},
      journal = {Neurotox Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, New Research Building WP13, Washington, DC 20057, USA. moccheti@georgetown.edu},
      year = {2012},
      volume = {21},
      number = {1},
      pages = {79--89},
      url = {http://dx.doi.org/10.1007/s12640-011-9279-2},
      doi = {http://doi.org/10.1007/s12640-011-9279-2}
    }
    
    Mocchetti, I., Campbell, L.A., Harry, G.J. & Avdoshina, V. When Human Immunodeficiency Virus Meets Chemokines and Microglia: Neuroprotection or Neurodegeneration? 2012 J Neuroimmune PharmacolSchool: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, Washington, DC, 20057, USA, moccheti@georgetown.edu.  DOI URL 
    Abstract: Chemokines are chemotactic cytokines that were originally discovered
    as promoters of leukocyte proliferation and mobility. In recent years,
    however, evidence has demonstrated constitutive expression of chemokines
    and chemokine receptors in a variety of cells in the central and
    peripheral nervous system and has proposed a role for chemokines
    in neurodegenerative diseases characterized by inflammation and microglia
    proliferation. In addition, chemokine receptors, and in particular
    CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV)
    infection of immunocompetent cells as well as microglia. Subsequently,
    HIV, through a variety of mechanisms, promotes synapto-dendritic
    alterations and neuronal loss that ultimately lead to motor and cognitive
    impairments. These events are accompanied by microglia activation.
    Nevertheless, a microglia-mediated mechanism of neuronal degeneration
    alone cannot fully explain some of the pathological features of HIV
    infected brain such as synaptic simplification. In this article,
    we present evidence that some of the microglia responses to HIV are
    beneficial and neuroprotective. These include the ability of microglia
    to release anti-inflammatory cytokines, to remove dying cells and
    to promote axonal sprouting.
    BibTeX:
    @article{Mocchetti2012,
      author = {Mocchetti, Italo and Campbell, Lee A. and Harry, G Jean and Avdoshina, Valeriya},
      title = {When Human Immunodeficiency Virus Meets Chemokines and Microglia: Neuroprotection or Neurodegeneration?},
      journal = {J Neuroimmune Pharmacol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, Washington, DC, 20057, USA, moccheti@georgetown.edu.},
      year = {2012},
      url = {http://dx.doi.org/10.1007/s11481-012-9353-4},
      doi = {http://doi.org/10.1007/s11481-012-9353-4}
    }
    
    Niedringhaus, M., Chen, X., Dzakpasu, R. & Conant, K. MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons. 2012 PLoS One
    Vol. 7(8), pp. e42631School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America. 
    DOI URL 
    Abstract: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases
    that are released from neurons in an activity dependent manner. Published
    studies suggest their activity is important to varied forms of learning
    and memory. At least one MMP can stimulate an increase in the size
    of dendritic spines, structures which represent the post synaptic
    component for a large number of glutamatergic synapses. This change
    may be associated with increased synaptic glutamate receptor incorporation,
    and an increased amplitude and/or frequency of ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate
    (AMPA) mini excitatory post-synaptic currents (EPSCs). An associated
    increase in the probability of action potential occurrence would
    be expected. While the mechanism(s) by which MMPs may influence synaptic
    structure and function are not completely understood, MMP dependent
    shedding of specific cell adhesion molecules (CAMs) could play an
    important role. CAMs are ideally positioned to be cleaved by synaptically
    released MMPs, and shed N terminal domains could potentially interact
    with previously unengaged integrins to stimulate dendritic actin
    polymerization with spine expansion. In the present study, we have
    used multielectrode arrays (MEAs) to investigate MMP and soluble
    CAM dependent changes in neuronal activity recorded from hippocampal
    cultures. We have focused on intercellular adhesion molecule-5 (ICAM-5)
    in particular, as this CAM is expressed on glutamatergic dendrites
    and shed in an MMP dependent manner. We show that chemical long-term
    potentiation (cLTP) evoked changes in recorded activity, and the
    dynamics of action potential bursts in particular, are altered by
    MMP inhibition. A blocking antibody to ?(1) integrins has a similar
    effect. We also show that the ectodomain of ICAM-5 can stimulate
    ?(1) integrin dependent increases in spike counts and burst number.
    These results support a growing body of literature suggesting that
    MMPs have important effects on neuronal excitability. They also support
    the possibility that MMP dependent shedding of specific synaptic
    CAMs can contribute to these effects.
    BibTeX:
    @article{Niedringhaus2012,
      author = {Niedringhaus, Mark and Chen, Xin and Dzakpasu, Rhonda and Conant, Katherine},
      title = {MMPs and soluble ICAM-5 increase neuronal excitability within in vitro networks of hippocampal neurons.},
      journal = {PLoS One},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, United States of America.},
      year = {2012},
      volume = {7},
      number = {8},
      pages = {e42631},
      url = {http://dx.doi.org/10.1371/journal.pone.0042631},
      doi = {http://doi.org/10.1371/journal.pone.0042631}
    }
    
    North, H.A., Clifford, M.A. & Donoghue, M.J. 'Til Eph Do Us Part': Intercellular Signaling via Eph Receptors and Ephrin Ligands Guides Cerebral Cortical Development from Birth Through Maturation. 2012 Cereb CortexSchool: Department of Biology and The Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20057, USA.  DOI URL 
    Abstract: Eph receptors, the largest family of surface-bound receptor tyrosine
    kinases and their ligands, the ephrins, mediate a wide variety of
    cellular interactions in most organ systems throughout both development
    and maturity. In the forming cerebral cortex, Eph family members
    are broadly and dynamically expressed in particular sets of cortical
    cells at discrete times. Here, we review the known functions of Eph-mediated
    intercellular signaling in the generation of progenitors, the migration
    of maturing cells, the differentiation of neurons, the formation
    of functional connections, and the choice between life and death
    during corticogenesis. In synthesizing these results, we posit a
    signaling paradigm in which cortical cells maintain a life history
    of Eph-mediated intercellular interactions that guides subsequent
    cellular decision-making.
    BibTeX:
    @article{North2012,
      author = {North, Hilary A. and Clifford, Meredith A. and Donoghue, Maria J.},
      title = {'Til Eph Do Us Part': Intercellular Signaling via Eph Receptors and Ephrin Ligands Guides Cerebral Cortical Development from Birth Through Maturation.},
      journal = {Cereb Cortex},
      school = {Department of Biology and The Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC 20057, USA.},
      year = {2012},
      url = {http://dx.doi.org/10.1093/cercor/bhs183},
      doi = {http://doi.org/10.1093/cercor/bhs183}
    }
    
    Rauschecker, J.P. Ventral and dorsal streams in the evolution of speech and language. 2012 Front Evol Neurosci
    Vol. 4, pp. 7School: University Medical Center, Washington DC, USA. 
    DOI URL 
    Abstract: The brains of humans and old-world monkeys show a great deal of anatomical
    similarity. The auditory cortical system, for instance, is organized
    into a ventral and a dorsal pathway in both species. A fundamental
    question with regard to the evolution of speech and language (as
    well as music) is whether human and monkey brains show principal
    differences in their organization (e.g., new pathways appearing as
    a result of a single mutation), or whether species differences are
    of a more subtle, quantitative nature. There is little doubt about
    a similar role of the ventral auditory pathway in both humans and
    monkeys in the decoding of spectrally complex sounds, which some
    authors have referred to as auditory object recognition. This includes
    the decoding of speech sounds ("speech perception") and their ultimate
    linking to meaning in humans. The originally presumed role of the
    auditory dorsal pathway in spatial processing, by analogy to the
    visual dorsal pathway, has recently been conceptualized into a more
    general role in sensorimotor integration and control. Specifically
    for speech, the dorsal processing stream plays a role in speech production
    as well as categorization of phonemes during on-line processing of
    speech.
    BibTeX:
    @article{Rauschecker2012,
      author = {Rauschecker, Josef P.},
      title = {Ventral and dorsal streams in the evolution of speech and language.},
      journal = {Front Evol Neurosci},
      school = { University Medical Center, Washington DC, USA.},
      year = {2012},
      volume = {4},
      pages = {7},
      url = {http://dx.doi.org/10.3389/fnevo.2012.00007},
      doi = {http://doi.org/10.3389/fnevo.2012.00007}
    }
    
    Riesenhuber, M. Learning-induced sharpening of neuronal tuning and adaptation: Not "mixed". 2012 Cogn Neurosci
    Vol. 3(3-4), pp. 242-243School: a Laboratory for Computational Cognitive Neuroscience, Department of Neuroscience , Georgetown University Medical Center , Washington , USA. 
    DOI URL 
    Abstract: Abstract Gotts et al. present an attractive model of how priming can
    arise from neuronal adaptation effects. Their very satisfying account
    helps to demystify adaptation effects. In fact, adaptation effects
    are even less mysterious than portrayed: While Gotts et al. state
    that "fMRI studies in humans that have attempted to evaluate sharpening
    of visual object representations with experience have … generated
    mixed results", referring to fMRI adaptation (fMRI-A) studies by
    our group and others, the results described in the cited papers are
    in fact entirely compatible, further establishing the usefulness
    of fMRI-A to probe neuronal tuning in humans.
    BibTeX:
    @article{Riesenhuber2012a,
      author = {Riesenhuber, Maximilian},
      title = {Learning-induced sharpening of neuronal tuning and adaptation: Not "mixed".},
      journal = {Cogn Neurosci},
      school = {a Laboratory for Computational Cognitive Neuroscience, Department of Neuroscience , Georgetown University Medical Center , Washington , USA.},
      year = {2012},
      volume = {3},
      number = {3-4},
      pages = {242--243},
      url = {http://dx.doi.org/10.1080/17588928.2012.689970},
      doi = {http://doi.org/10.1080/17588928.2012.689970}
    }
    
    Riesenhuber, M. Getting a handle on how the brain generates complexity. 2012 Network
    Vol. 23(3), pp. 123-127School: Laboratory for Computational Cognitive Neuroscience, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. mr287@georgetown.edu 
    DOI URL 
    Abstract: Sensory processing in cortex across modalities appears to rely on
    a "simple-to-complex" hierarchical computational strategy in which
    neurons at later levels in the hierarchy combine inputs from earlier
    levels to create more complex neuronal selectivities. The specifics
    of this process are still poorly understood, however. In this issue
    of Network, Plebe shows how computational modeling of experimental
    data on neuronal tuning in secondary visual cortex can help us understand
    how the brain increases neuronal tuning complexity across the visual
    cortical hierarchy.
    BibTeX:
    @article{Riesenhuber2012,
      author = {Riesenhuber, Maximilian},
      title = {Getting a handle on how the brain generates complexity.},
      journal = {Network},
      school = {Laboratory for Computational Cognitive Neuroscience, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. mr287@georgetown.edu},
      year = {2012},
      volume = {23},
      number = {3},
      pages = {123--127},
      url = {http://dx.doi.org/10.3109/0954898X.2012.711918},
      doi = {http://doi.org/10.3109/0954898X.2012.711918}
    }
    
    Rozeboom, A.M. & Pak, D.T.S. Identification and functional characterization of polo-like kinase 2 autoregulatory sites. 2012 Neuroscience
    Vol. 202, pp. 147-157School: Department of Pharmacology and Physiology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Polo family kinases play important roles in cellular proliferation
    as well as neuronal synaptic plasticity. However, the posttranslational
    regulation of these kinases is not fully understood. Here, we identified
    several novel Plk2 phosphorylation sites stimulated by Plk2 itself.
    By site-directed mutagenesis, we uncovered three additional hyperactivating
    Plk2 mutations as well as a series of residues regulating Plk2 steady-state
    expression level. Because of the established role of Plk2 in homeostatic
    negative control of excitatory synaptic strength, these phosphorylation
    sites could play an important role in the rapid activation, expansion,
    and prolongation of Plk2 signaling in this process.
    BibTeX:
    @article{Rozeboom2012,
      author = {Rozeboom, A. M. and Pak, D T S.},
      title = {Identification and functional characterization of polo-like kinase 2 autoregulatory sites.},
      journal = {Neuroscience},
      school = {Department of Pharmacology and Physiology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057-1464, USA.},
      year = {2012},
      volume = {202},
      pages = {147--157},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2011.11.003},
      doi = {http://doi.org/10.1016/j.neuroscience.2011.11.003}
    }
    
    Scholz, S.W., Mhyre, T., Ressom, H., Shah, S. & Federoff, H.J. Genomics and bioinformatics of Parkinson's disease. 2012 Cold Spring Harb Perspect Med
    Vol. 2(7), pp. a009449School: Department of Neuroscience, Georgetown University, Washington, DC 20057. 
    DOI URL 
    Abstract: Within the last two decades, genomics and bioinformatics have profoundly
    impacted our understanding of the molecular mechanisms of Parkinson's
    disease (PD). From the description of the first PD gene in 1997 until
    today, we have witnessed the emergence of new technologies that have
    revolutionized our concepts to identify genetic mechanisms implicated
    in human health and disease. Driven by the publication of the human
    genome sequence and followed by the description of detailed maps
    for common genetic variability, novel applications to rapidly scrutinize
    the entire genome in a systematic, cost-effective manner have become
    a reality. As a consequence, about 30 genetic loci have been unequivocally
    linked to the pathogenesis of PD highlighting essential molecular
    pathways underlying this common disorder. Herein we discuss how neurogenomics
    and bioinformatics are applied to dissect the nature of this complex
    disease with the overall aim of developing rational therapeutic interventions.
    BibTeX:
    @article{Scholz2012,
      author = {Scholz, Sonja W. and Mhyre, Tim and Ressom, Habtom and Shah, Salim and Federoff, Howard J.},
      title = {Genomics and bioinformatics of Parkinson's disease.},
      journal = {Cold Spring Harb Perspect Med},
      school = {Department of Neuroscience, Georgetown University, Washington, DC 20057.},
      year = {2012},
      volume = {2},
      number = {7},
      pages = {a009449},
      url = {http://dx.doi.org/10.1101/cshperspect.a009449},
      doi = {http://doi.org/10.1101/cshperspect.a009449}
    }
    
    Seydell-Greenwald, A., Leaver, A.M., Turesky, T.K., Morgan, S., Kim, H.J. & Rauschecker, J.P. Functional MRI evidence for a role of ventral prefrontal cortex in tinnitus. 2012 Brain Res
    Vol. 1485, pp. 22-39School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd. NW, Washington, DC 20007, USA. as2266@georgetown.edu 
    DOI URL 
    Abstract: It has long been known that subjective tinnitus, a constant or intermittent
    phantom sound perceived by 10 to 15% of the adult population, is
    not a purely auditory phenomenon but is also tied to limbic-related
    brain regions. Supporting evidence comes from data indicating that
    stress and emotion can modulate tinnitus, and from brain imaging
    studies showing functional and anatomical differences in limbic-related
    brain regions of tinnitus patients and controls. Recent studies from
    our lab revealed altered blood oxygen level-dependent (BOLD) responses
    to stimulation at the tinnitus frequency in the ventral striatum
    (specifically, the nucleus accumbens) and gray-matter reductions
    (i.e., anatomical changes) in ventromedial prefrontal cortex (vmPFC),
    of tinnitus patients compared to controls. The present study extended
    these findings by demonstrating functional differences in vmPFC between
    20 tinnitus patients and 20 age-matched controls. Importantly, the
    observed BOLD response in vmPFC was positively correlated with tinnitus
    characteristics such as subjective loudness and the percent of time
    during which the tinnitus was perceived, whereas correlations with
    tinnitus handicap inventory scores and other variables known to be
    affected in tinnitus (e.g., depression, anxiety, noise sensitivity,
    hearing loss) were weaker or absent. This suggests that the observed
    group differences are indeed related to the strength of the tinnitus
    percept and not to an affective reaction to tinnitus. The results
    further corroborate vmPFC as a region of high interest for tinnitus
    research.This article is part of a Special Issue entitled: Tinnitus
    Neuroscience.
    BibTeX:
    @article{Seydell-Greenwald2012,
      author = {Seydell-Greenwald, Anna and Leaver, Amber M. and Turesky, Ted K. and Morgan, Susan and Kim, Hung J. and Rauschecker, Josef P.},
      title = {Functional MRI evidence for a role of ventral prefrontal cortex in tinnitus.},
      journal = {Brain Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd. NW, Washington, DC 20007, USA. as2266@georgetown.edu},
      year = {2012},
      volume = {1485},
      pages = {22--39},
      url = {http://dx.doi.org/10.1016/j.brainres.2012.08.052},
      doi = {http://doi.org/10.1016/j.brainres.2012.08.052}
    }
    
    Seydell-Greenwald, A. & Schmidt, T. Rapid activation of motor responses by illusory contours. 2012 J Exp Psychol Hum Percept Perform
    Vol. 38(5), pp. 1168-1182School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. as2266@georgetown.edu 
    DOI URL 
    Abstract: Whereas physiological studies indicate that illusory contours (ICs)
    are signaled in early visual areas at short latencies, behavioral
    studies are divided as to whether IC processing can proceed in a
    fast, automatic, bottom-up manner or whether it requires extensive
    top-down intracortical feedback or even awareness and cognition.
    Here, we employ a response priming paradigm to assess two measures
    of IC processing using identical stimuli: response priming by ICs,
    which can occur independently of visual awareness, and a measure
    of visual awareness of the ICs. In three experiments, participants
    responded to the orientation of illusory and real-contour targets
    preceded by illusory and real-contour primes at stimulus-onset asynchronies
    from 35 to 106 ms. Both illusory and real-contour targets were strongly
    primed by ICs, and this effect was independent of prime visibility.
    The effect was fully present in the fastest responses and cannot
    be explained by responses to stimulus features other than the ICs.
    Results indicate that ICs, regardless of whether they are consciously
    perceived, activate fast motor responses, indicating that they are
    processed without time-consuming intracortical feedback. We conclude
    that conflicting studies were based on qualitatively different measures
    of IC processing, some depending on visual awareness and others independent
    of it.
    BibTeX:
    @article{Seydell-Greenwald2012a,
      author = {Seydell-Greenwald, Anna and Schmidt, Thomas},
      title = {Rapid activation of motor responses by illusory contours.},
      journal = {J Exp Psychol Hum Percept Perform},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. as2266@georgetown.edu},
      year = {2012},
      volume = {38},
      number = {5},
      pages = {1168--1182},
      url = {http://dx.doi.org/10.1037/a0028767},
      doi = {http://doi.org/10.1037/a0028767}
    }
    
    Ullrich, L.E., Krafnick, A.J., Dumanis, S.B. & Forcelli, P.A. Drugs, the brain, and behavior: a graduate student-run comprehensive course in neuroscience. 2012 J Undergrad Neurosci Educ
    Vol. 10(2), pp. A105-A112School: Interdisciplinary Program in Neuroscience; ; Department of Neurology; 
     
    Abstract: Drugs, the Brain, and Behavior is an interdisciplinary two-semester
    upper level course at Georgetown University designed to expose undergraduate
    and graduate students to broad areas of the neurosciences, to promote
    the development of scientific literacy in these students, and to
    provide pedagogical experience for Ph.D. students in the Interdisciplinary
    Program in Neuroscience (IPN) at all stages of training. Drugs, the
    Brain, and Behavior fulfills these goals through a unique model of
    student-teaching. This lecture-based, team-taught course is completely
    run and taught by Ph.D. students in the IPN. It is designed to gradually
    increase the teaching duties of new instructors, providing a structured
    setting for them to develop their pedagogical skills. We encourage
    scientific literacy in our students through the incorporation of
    primary literature and experimental results throughout the course.
    The strategies we have employed have increased student confidence
    on a variety of measures of scientific literacy. While running a
    team-taught course, we have also developed several strategies for
    coordinating team-taught courses within semesters and across years,
    which could easily be adapted to other courses.
    BibTeX:
    @article{Ullrich2012,
      author = {Ullrich, Lauren E. and Krafnick, Anthony J. and Dumanis, Sonya B. and Forcelli, Patrick A.},
      title = {Drugs, the brain, and behavior: a graduate student-run comprehensive course in neuroscience.},
      journal = {J Undergrad Neurosci Educ},
      school = {Interdisciplinary Program in Neuroscience; ; Department of Neurology;},
      year = {2012},
      volume = {10},
      number = {2},
      pages = {A105--A112}
    }
    
    Washington, P.M., Forcelli, P.A., Wilkins, T., Zapple, D.N., Parsadanian, M. & Burns, M.P. The Effect of Injury Severity on Behavior: A Phenotypic Study of Cognitive and Emotional Deficits after Mild, Moderate, and Severe Controlled Cortical Impact Injury in Mice. 2012 J NeurotraumaSchool: 1 Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center , Washington, D.C.  DOI URL 
    Abstract: Abstract Traumatic brain injury (TBI) can cause a broad array of behavioral
    problems including cognitive and emotional deficits. Human studies
    comparing neurobehavioral outcomes after TBI suggest that cognitive
    impairments increase with injury severity, but emotional problems
    such as anxiety and depression do not. To determine whether cognitive
    and emotional impairments increase as a function of injury severity
    we exposed mice to sham, mild, moderate, or severe controlled cortical
    impact (CCI) and evaluated performance on a variety of neurobehavioral
    tests in the same animals before assessing lesion volume as a histological
    measure of injury severity. Increasing cortical impact depth successfully
    produced lesions of increasing severity in our model. We found that
    cognitive impairments in the Morris water maze increased with injury
    severity, as did the degree of contralateral torso flexion, a measure
    of unilateral striatal damage. TBI also caused deficits in emotional
    behavior as quantified in the forced swim test, elevated-plus maze,
    and prepulse inhibition of acoustic startle, but these deficits were
    not dependent on injury severity. Stepwise regression analyses revealed
    that Morris water maze performance and torso flexion predicted the
    majority of the variability in lesion volume. In summary, we find
    that cognitive deficits increase in relation to injury severity,
    but emotional deficits do not. Our data suggest that the threshold
    for emotional changes after experimental TBI is low, with no variation
    in behavioral deficits seen between mild and severe brain injury.
    BibTeX:
    @article{Washington2012,
      author = {Washington, Patricia M. and Forcelli, Patrick A. and Wilkins, Tiffany and Zapple, David N. and Parsadanian, Maia and Burns, Mark P.},
      title = {The Effect of Injury Severity on Behavior: A Phenotypic Study of Cognitive and Emotional Deficits after Mild, Moderate, and Severe Controlled Cortical Impact Injury in Mice.},
      journal = {J Neurotrauma},
      school = {1 Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center , Washington, D.C.},
      year = {2012},
      url = {http://dx.doi.org/10.1089/neu.2012.2456},
      doi = {http://doi.org/10.1089/neu.2012.2456}
    }
    
    Whittaker, M.T., Zai, L.J., Lee, H.J., Pajoohesh-Ganji, A., Wu, J., Sharp, A., Wyse, R. & Wrathall, J.R. GGF2 (Nrg1-?3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury. 2012 Glia
    Vol. 60(2), pp. 281-294School: Department of Neuroscience, Georgetown University, Washington, District of Columbia 20057, USA. 
    DOI URL 
    Abstract: The adult spinal cord contains a pool of endogenous glial precursor
    cells, which spontaneously respond to spinal cord injury (SCI) with
    increased proliferation. These include oligodendrocyte precursor
    cells that express the NG2 proteoglycan and can differentiate into
    mature oligodendrocytes. Thus, a potential approach for SCI treatment
    is to enhance the proliferation and differentiation of these cells
    to yield more functional mature glia and improve remyelination of
    surviving axons. We previously reported that soluble glial growth
    factor 2 (GGF2)- and basic fibroblast growth factor 2 (FGF2)-stimulated
    growth of NG2(+) cells purified from injured spinal cord in primary
    culture. This study examines the effects of systemic administration
    of GGF2 and/or FGF2 after standardized contusive SCI in vivo in both
    rat and mouse models. In Sprague-Dawley rats, 1 week of GGF2 administration,
    beginning 24 h after injury, enhanced NG2(+) cell proliferation,
    oligodendrogenesis, chronic white matter at the injury epicenter,
    and recovery of hind limb function. In 2',3'-cyclic-nucleotide 3'-phosphodiesterase-enhanced
    green fluorescent protein mice, GGF2 treatment resulted in increased
    oligodendrogenesis and improved functional recovery, as well as elevated
    expression of the stem cell transcription factor Sox2 by oligodendrocyte
    lineage cells. Although oligodendrocyte number was increased chronically
    after SCI in GGF2-treated mice, no evidence of increased white matter
    was detected. However, GGF2 treatment significantly increased levels
    of P0 protein-containing peripheral myelin, produced by Schwann cells
    that infiltrate the injured spinal cord. Our results suggest that
    GGF2 may have therapeutic potential for SCI by enhancing endogenous
    recovery processes in a clinically relevant time frame.
    BibTeX:
    @article{Whittaker2012,
      author = {Whittaker, Matthew T. and Zai, Laila J. and Lee, Hyun Joon and Pajoohesh-Ganji, Ahdeah and Wu, Junfang and Sharp, April and Wyse, Ransom and Wrathall, Jean R.},
      title = {GGF2 (Nrg1-?3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury.},
      journal = {Glia},
      school = {Department of Neuroscience, Georgetown University, Washington, District of Columbia 20057, USA.},
      year = {2012},
      volume = {60},
      number = {2},
      pages = {281--294},
      url = {http://dx.doi.org/10.1002/glia.21262},
      doi = {http://doi.org/10.1002/glia.21262}
    }
    
    Wurzman, R. & Giordano, J. Differential susceptibility to plasticity: a 'missing link' between gene-culture co-evolution and neuropsychiatric spectrum disorders? 2012 BMC Med
    Vol. 10, pp. 37School: Interdisciplinary Neuroscience Program, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Br?ne's proposal that erstwhile 'vulnerability' genes need to be reconsidered
    as 'plasticity' genes, given the potential for certain environments
    to yield increased positive function in the same domain as potential
    dysfunction, has implications for psychiatric nosology as well as
    a more dynamic understanding of the relationship between genes and
    culture. In addition to validating neuropsychiatric spectrum disorder
    nosologies by calling for similar methodological shifts in gene-environment-interaction
    studies, Br?ne's position elevates the importance of environmental
    contexts - inclusive of socio-cultural variables - as mechanisms
    that contribute to clinical presentation. We assert that when models
    of susceptibility to plasticity and neuropsychiatric spectrum disorders
    are concomitantly considered, a new line of inquiry emerges into
    the co-evolution and co-determination of socio-cultural contexts
    and endophenotypes. This presents potentially unique opportunities,
    benefits, challenges, and responsibilities for research and practice
    in psychiatry. Please see related manuscript: http://www.biomedcentral.com/1741-7015/10/38.
    BibTeX:
    @article{Wurzman2012,
      author = {Wurzman, Rachel and Giordano, James},
      title = {Differential susceptibility to plasticity: a 'missing link' between gene-culture co-evolution and neuropsychiatric spectrum disorders?},
      journal = {BMC Med},
      school = {Interdisciplinary Neuroscience Program, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2012},
      volume = {10},
      pages = {37},
      url = {http://dx.doi.org/10.1186/1741-7015-10-37},
      doi = {http://doi.org/10.1186/1741-7015-10-37}
    }
    
    Yerys, B.E., Ruiz, E., Strang, J., Sokoloff, J., Kenworthy, L. & Vaidya, C.J. Modulation of attentional blink with emotional faces in typical development and in autism spectrum disorders. 2012 J Child Psychol PsychiatrySchool: Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA Center for Autism Spectrum Disorders, Children's National Medical Center, Washington, DC Children's Research Institute, Children's National Medical Center, Washington, DC Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC Department of Psychology, Georgetown University, Washington, DC, USA.  DOI URL 
    Abstract: Background:? The attentional blink (AB) phenomenon was used to assess
    the effect of emotional information on early visual attention in
    typically developing (TD) children and children with autism spectrum
    disorders (ASD). The AΒ effect is the momentary perceptual unawareness
    that follows target identification in a rapid serial visual processing
    stream. It is abolished or reduced for emotional stimuli, indicating
    that emotional information has privileged access to early visual
    attention processes. Methods:? We examined the AΒ effect for faces
    with neutral and angry facial expressions in 8- to 14-year-old children
    with and without an ASD diagnosis. Results:? Children with ASD exhibited
    the same magnitude AΒ effect as TD children for both neutral and
    angry faces. Conclusions:? Early visual attention to emotional facial
    expressions was preserved in children with ASD.
    BibTeX:
    @article{Yerys2012,
      author = {Yerys, Benjamin E. and Ruiz, Ericka and Strang, John and Sokoloff, Jennifer and Kenworthy, Lauren and Vaidya, Chandan J.},
      title = {Modulation of attentional blink with emotional faces in typical development and in autism spectrum disorders.},
      journal = {J Child Psychol Psychiatry},
      school = {Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA Center for Autism Spectrum Disorders, Children's National Medical Center, Washington, DC Children's Research Institute, Children's National Medical Center, Washington, DC Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC Department of Psychology, Georgetown University, Washington, DC, USA.},
      year = {2012},
      url = {http://dx.doi.org/10.1111/jcpp.12013},
      doi = {http://doi.org/10.1111/jcpp.12013}
    }
    
    Avdoshina, V., Becker, J., Campbell, L.A., Parsadanian, M., Mhyre, T., Tessarollo, L. & Mocchetti, I. Neurotrophins modulate the expression of chemokine receptors in the brain. 2011 J Neurovirol
    Vol. 17(1), pp. 58-62School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: In the central nervous system, chemokines are primarily mediators
    of inflammatory processes. Their receptors, in particular, CXCR4
    and CCR5, serve as co-factors along with CD4 that permit Human immunodeficiency
    virus-1 (HIV) infection. Moreover, experimental evidence has shown
    that CXCR4 and CCR5 mediate the neurotoxic effects of the HIV envelope
    protein gp120, suggesting that these receptors could also promote
    the neuropathogenesis observed in HIV-positive individuals. Therefore,
    a better understanding of the molecular mechanisms governing the
    expression of chemokine receptors in the brain may lead to improved
    therapies that reduce HIV neurotoxicity. This study presents evidence
    that the expression of chemokine receptors in the brain is modulated
    by two neurotrophins in an area-specific manner. This new evidence
    suggests that the neurotrophins may be an adjunct therapy to reduce
    HIV-mediated neuronal injury evoked by chemokine receptor activation.
    BibTeX:
    @article{Avdoshina2011a,
      author = {Valeriya Avdoshina and Jody Becker and Lee A Campbell and Maia Parsadanian and Timothy Mhyre and Lino Tessarollo and Italo Mocchetti},
      title = {Neurotrophins modulate the expression of chemokine receptors in the brain.},
      journal = {J Neurovirol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2011},
      volume = {17},
      number = {1},
      pages = {58--62},
      url = {http://dx.doi.org/10.1007/s13365-010-0004-3},
      doi = {http://doi.org/10.1007/s13365-010-0004-3}
    }
    
    Avdoshina, V., Garzino-Demo, A., Bachis, A., Monaco, M.C., Maki, P.M., Tractenberg, R.E., Liu, C., Young, M.A. & Mocchetti, I. HIV-1 decreases the levels of neurotrophins in human lymphocytes. 2011 AIDS
    Vol. 25(8), pp. 1126-1128School: aDepartment of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA bDepartment of Microbiology and Immunology, Institute of Human Virology, University of Maryland, Baltimore, USA cLaboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke/National Institute of Health, Bethesda, Maryland, USA dDepartments of Psychiatry and Psychology, University of Illinois at Chicago, Chicago, Illinois, USA eDepartment of Neurology, USA fDepartment of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: Neurotrophins control cell survival. Therefore, we examined whether
    HIV-1 reduces neurotrophin levels. Serum of HIV-positive individuals
    exhibited lower concentrations of brain-derived neurotrophic factor
    (BDNF), but not of other neurotrophins, than HIV-negative individuals.
    In addition, R5 and X4 strains of HIV-1 decreased BDNF expression
    in T cells. Our results support the hypothesis that reduced levels
    of BDNF may be a risk factor for T-cell apoptosis and for neurological
    complications associated with HIV-1 infection.
    BibTeX:
    @article{Avdoshina2011,
      author = {Valeriya Avdoshina and Alfredo Garzino-Demo and Alessia Bachis and Maria Cg Monaco and Pauline M Maki and Rochelle E Tractenberg and Chenglong Liu and Mary A Young and Italo Mocchetti},
      title = {HIV-1 decreases the levels of neurotrophins in human lymphocytes.},
      journal = {AIDS},
      school = {aDepartment of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA bDepartment of Microbiology and Immunology, Institute of Human Virology, University of Maryland, Baltimore, USA cLaboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke/National Institute of Health, Bethesda, Maryland, USA dDepartments of Psychiatry and Psychology, University of Illinois at Chicago, Chicago, Illinois, USA eDepartment of Neurology, USA fDepartment of Medicine, Georgetown University Medical Center, Washington, District of Columbia, USA.},
      year = {2011},
      volume = {25},
      number = {8},
      pages = {1126--1128},
      url = {http://dx.doi.org/10.1097/QAD.0b013e32834671b3},
      doi = {http://doi.org/10.1097/QAD.0b013e32834671b3}
    }
    
    Béraud, D., Twomey, M., Bloom, B., Mittereder, A., Ton, V., Neitzke, K., Chasovskikh, S., Mhyre, T.R. & Maguire-Zeiss, K.A. α-Synuclein Alters Toll-Like Receptor Expression. 2011 Front Neurosci
    Vol. 5, pp. 80School: Interdisciplinary Program in Neuroscience, Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: Parkinson's disease, an age-related neurodegenerative disorder, is characterized by the loss of dopamine neurons in the substantia nigra, the accumulation of α-synuclein in Lewy bodies and neurites, and neuroinflammation. While the exact etiology of sporadic Parkinson's disease remains elusive, a growing body of evidence suggests that misfolded α-synuclein promotes inflammation and oxidative stress resulting in neurodegeneration. α-synuclein has been directly linked to microglial activation in vitro and increased numbers of activated microglia have been reported in an α-synuclein overexpressing mouse model prior to neuronal loss. However, the mechanism by which α-synuclein incites microglial activation has not been fully described. Microglial activation is governed in part, by pattern recognition receptors that detect foreign material and additionally recognize changes in homeostatic cellular conditions. Upon proinflammatory pathway initiation, activated microglia contribute to oxidative stress through release of cytokines, nitric oxide, and other reactive oxygen species, which may adversely impact adjacent neurons. Here we show that microglia are directly activated by α-synuclein in a classical activation pathway that includes alterations in the expression of toll-like receptors. These data suggest that α-synuclein can act as a danger-associated molecular pattern.
    BibTeX:
    @article{BeraudTwomeyBloomEtAl2011,
      author = {Béraud, Dawn and Twomey, Margaret and Bloom, Benjamin and Mittereder, Andrew and Ton, Vy and Neitzke, Katherine and Chasovskikh, Sergey and Mhyre, Timothy R. and Maguire-Zeiss, Kathleen A.},
      title = {$-Synuclein Alters Toll-Like Receptor Expression.},
      journal = {Front Neurosci},
      school = {Interdisciplinary Program in Neuroscience, Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA.},
      year = {2011},
      volume = {5},
      pages = {80},
      url = {http://dx.doi.org/10.3389/fnins.2011.00080},
      doi = {http://doi.org/10.3389/fnins.2011.00080}
    }
    
    Babus, L.W., Little, E.M., Keenoy, K.E., Minami, S.S., Chen, E., Song, J.M., Caviness, J., Koo, S.-Y., Pak, D.T.S., Rebeck, G.W., Turner, R.S. & Hoe, H.-S. Decreased dendritic spine density and abnormal spine morphology in Fyn knockout mice. 2011 Brain Res
    Vol. 1415, pp. 96-102School: ir Road NW, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Fyn is a Src-family tyrosine kinase that affects long term potentiation
    (LTP), synapse formation, and learning and memory. Fyn is also implicated
    in dendritic spine formation both in vitro and in vivo. However,
    whether Fyn's regulation of dendritic spine formation is brain-region
    specific and age-dependent is unknown. In the present study, we systematically
    examined whether Fyn altered dendritic spine density and morphology
    in the cortex and hippocampus and if these effects were age-dependent.
    We found that Fyn knockout mice trended toward a decrease in dendritic
    spine density in cortical layers II/III, but not in the hippocampus,
    at 1 month of age. Additionally, Fyn knockout mice had significantly
    decreased dendritic spine density in both the cortex and hippocampus
    at 3 months and 1 year, and Fyn's effect on dendritic spine density
    was age-dependent in the hippocampus. Moreover, Fyn knockout mice
    had wider spines at the three time points (1 month, 3 months, 1 year)
    in the cortex. These findings suggest that Fyn regulates dendritic
    spine number and morphology over time and provide further support
    for Fyn's role in maintaining proper synaptic function in vivo.
    BibTeX:
    @article{Babus2011,
      author = {Babus, Lenard W. and Little, Elizabeth M. and Keenoy, Kathleen E. and Minami, S Sakura and Chen, Eric and Song, Jung Min and Caviness, Juliet and Koo, So-Yeon and Pak, Daniel T S. and Rebeck, G William and Turner, R Scott and Hoe, Hyang-Sook},
      title = {Decreased dendritic spine density and abnormal spine morphology in Fyn knockout mice.},
      journal = {Brain Res},
      school = {ir Road NW, Washington, DC 20057-1464, USA.},
      year = {2011},
      volume = {1415},
      pages = {96--102},
      url = {http://dx.doi.org/10.1016/j.brainres.2011.07.059},
      doi = {http://doi.org/10.1016/j.brainres.2011.07.059}
    }
    
    Byrnes, K.R., Washington, P.M., Knoblach, S.M., Hoffman, E. & Faden, A.I. Delayed inflammatory mRNA and protein expression after spinal cord injury. 2011 J Neuroinflammation
    Vol. 8, pp. 130School: Department of Neuroscience, Georgetown University Medical Center, NW, Washington, DC (20057), USA. kbyrnes@usuhs.mil 
    DOI URL 
    Abstract: Spinal cord injury (SCI) induces secondary tissue damage that is associated
    with inflammation. We have previously demonstrated that inflammation-related
    gene expression after SCI occurs in two waves - an initial cluster
    that is acutely and transiently up-regulated within 24 hours, and
    a more delayed cluster that peaks between 72 hours and 7 days. Here
    we extend the microarray analysis of these gene clusters up to 6
    months post-SCI.Adult male rats were subjected to mild, moderate
    or severe spinal cord contusion injury at T9 using a well-characterized
    weight-drop model. Tissue from the lesion epicenter was obtained
    4 hours, 24 hours, 7 days, 28 days, 3 months or 6 months post-injury
    and processed for microarray analysis and protein expression.Anchor
    gene analysis using C1qB revealed a cluster of genes that showed
    elevated expression through 6 months post-injury, including galectin-3,
    p22PHOX, gp91PHOX, CD53 and progranulin. The expression of these
    genes occurred primarily in microglia/macrophage cells and was confirmed
    at the protein level using both immunohistochemistry and western
    blotting. As p22PHOX and gp91PHOX are components of the NADPH oxidase
    enzyme, enzymatic activity and its role in SCI were assessed and
    NADPH oxidase activity was found to be significantly up-regulated
    through 6 months post-injury. Further, treating rats with the nonspecific,
    irreversible NADPH oxidase inhibitor diphenylene iodinium (DPI) reduced
    both lesion volume and expression of chronic gene cluster proteins
    one month after trauma.These data demonstrate that inflammation-related
    genes are chronically up-regulated after SCI and may contribute to
    further tissue loss.
    BibTeX:
    @article{Byrnes2011,
      author = {Byrnes, Kimberly R. and Washington, Patricia M. and Knoblach, Susan M. and Hoffman, Eric and Faden, Alan I.},
      title = {Delayed inflammatory mRNA and protein expression after spinal cord injury.},
      journal = {J Neuroinflammation},
      school = {Department of Neuroscience, Georgetown University Medical Center, NW, Washington, DC (20057), USA. kbyrnes@usuhs.mil},
      year = {2011},
      volume = {8},
      pages = {130},
      url = {http://dx.doi.org/10.1186/1742-2094-8-130},
      doi = {http://doi.org/10.1186/1742-2094-8-130}
    }
    
    Chevillet, M., Riesenhuber, M. & Rauschecker, J.P. Functional correlates of the anterolateral processing hierarchy in human auditory cortex. 2011 J Neurosci
    Vol. 31(25), pp. 9345-9352School: Laboratories of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Converging evidence supports the hypothesis that an anterolateral
    processing pathway mediates sound identification in auditory cortex,
    analogous to the role of the ventral cortical pathway in visual object
    recognition. Studies in nonhuman primates have characterized the
    anterolateral auditory pathway as a processing hierarchy, composed
    of three anatomically and physiologically distinct initial stages:
    core, belt, and parabelt. In humans, potential homologs of these
    regions have been identified anatomically, but reliable and complete
    functional distinctions between them have yet to be established.
    Because the anatomical locations of these fields vary across subjects,
    investigations of potential homologs between monkeys and humans require
    these fields to be defined in single subjects. Using functional MRI,
    we presented three classes of sounds (tones, band-passed noise bursts,
    and conspecific vocalizations), equivalent to those used in previous
    monkey studies. In each individual subject, three regions showing
    functional similarities to macaque core, belt, and parabelt were
    readily identified. Furthermore, the relative sizes and locations
    of these regions were consistent with those reported in human anatomical
    studies. Our results demonstrate that the functional organization
    of the anterolateral processing pathway in humans is largely consistent
    with that of nonhuman primates. Because our scanning sessions last
    only 15 min/subject, they can be run in conjunction with other scans.
    This will enable future studies to characterize functional modules
    in human auditory cortex at a level of detail previously possible
    only in visual cortex. Furthermore, the approach of using identical
    schemes in both humans and monkeys will aid with establishing potential
    homologies between them.
    BibTeX:
    @article{Chevillet2011,
      author = {Chevillet, Mark and Riesenhuber, Maximilian and Rauschecker, Josef P.},
      title = {Functional correlates of the anterolateral processing hierarchy in human auditory cortex.},
      journal = {J Neurosci},
      school = {Laboratories of Integrative Neuroscience and Cognition, Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2011},
      volume = {31},
      number = {25},
      pages = {9345--9352},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.1448-11.2011},
      doi = {http://doi.org/10.1523/JNEUROSCI.1448-11.2011}
    }
    
    Conant, K., Lonskaya, I., Szklarczyk, A., Krall, C., Steiner, J., Maguire-Zeiss, K. & Lim, S.T. Methamphetamine-associated cleavage of the synaptic adhesion molecule intercellular adhesion molecule-5. 2011 J Neurochem
    Vol. 118(4), pp. 521-532School: The Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20007, USA. kec84@georgetown.edu 
    DOI URL 
    Abstract: Methamphetamine (MA) is a highly addictive psychostimulant that, used
    in excess, may be neurotoxic. Although the mechanisms that underlie
    its addictive potential are not completely understood, in animal
    models matrix metalloproteinase (MMP) inhibitors can reduce behavioral
    correlates of addiction. In addition, evidence from genome-wide association
    studies suggests that polymorphisms in synaptic cell-adhesion molecules
    (CAMs), known MMP substrates, are linked to addictive potential in
    humans. In the present study, we examined the ability of MA to stimulate
    cleavage of intercellular adhesion molecule-5 (ICAM-5), a synaptic
    CAM expressed on dendritic spines in the telencephalon. Previous
    studies have shown that shedding of ICAM-5 is associated with maturation
    of dendritic spines, and that MMP-dependent shedding occurs with
    long term potentiation. Herein, we show that MA stimulates ectodomain
    cleavage of ICAM-5 in vitro, and that this is abrogated by a broad
    spectrum MMP inhibitor. We also show that an acute dose of MA, administered
    in vivo, is associated with cleavage of ICAM-5 in murine hippocampus
    and striatum. This occurs within 6?h and is accompanied by an increase
    in MMP-9 protein. In related experiments, we examined the potential
    consequences of ICAM-5 shedding. We demonstrate that the ICAM-5 ectodomain
    can interact with ?(1) integrins, and that it can stimulate ?(1)
    integrin-dependent phosphorylation of cofilin, an event that has
    previously been linked to MMP-dependent spine maturation. Together
    these data support an emerging appreciation of MMPs as effectors
    of synaptic plasticity and suggest a mechanism by which MA may influence
    the same.
    BibTeX:
    @article{Conant2011,
      author = {Conant, Katherine and Lonskaya, Irina and Szklarczyk, Arek and Krall, Caroline and Steiner, Joseph and Maguire-Zeiss, Kathleen and Lim, Seung T.},
      title = {Methamphetamine-associated cleavage of the synaptic adhesion molecule intercellular adhesion molecule-5.},
      journal = {J Neurochem},
      school = {The Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20007, USA. kec84@georgetown.edu},
      year = {2011},
      volume = {118},
      number = {4},
      pages = {521--532},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2010.07153.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2010.07153.x}
    }
    
    Crowe, S.L., Tsukerman, S., Gale, K., Jorgensen, T.J. & Kondratyev, A.D. Phosphorylation of Histone H2A.X as an Early Marker of Neuronal Endangerment following Seizures in the Adult Rat Brain. 2011 J Neurosci
    Vol. 31(21), pp. 7648-7656School: Interdisciplinary Program in Neuroscience and Departments of Pharmacology, Pediatrics, and Radiation Medicine, Georgetown University, Washington, DC 20057. 
    DOI URL 
    Abstract: The phosphorylated form of histone H2A.X (?-H2AX) is a well documented
    early, sensitive, and selective marker of DNA double-strand breaks
    (DSBs). Previously, we found that excessive glutamatergic activity
    increased ?-H2AX in neurons in vitro. Here, we evaluated ?-H2AX formation
    in the adult rat brain following neuronal excitation evoked by seizure
    activity in vivo. We found that brief, repeated electroconvulsive
    shock (ECS)-induced seizures (three individual seizures within 60
    min) did not trigger an increase ?-H2AX immunostaining. In contrast,
    a cluster of 5-7 individual seizures evoked by kainic acid (KA) rapidly
    (within 30 min) induced ?-H2AX in multiple neuronal populations in
    hippocampus and entorhinal cortex. This duration of seizure activity
    is well below threshold for induction of neuronal cell death, indicating
    that the ?-H2AX increase occurs in response to sublethal insults.
    Moreover, an increase in ?-H2AX was seen in dentate granule cells,
    which are resistant to cell death caused by KA-evoked seizures. With
    as little as a 5 min duration of status epilepticus (SE), ?-H2AX
    increased in CA1, CA3, and entorhinal cortex to a greater extent
    than that observed after the clusters of individual seizures, with
    still greater increases after 120 min of SE. Our findings provide
    the first direct demonstration that DNA DSB damage occurs in vivo
    in the brain following seizures. Furthermore, we found that the ?-H2AX
    increase caused by 120 min of SE was prevented by neuroprotective
    preconditioning with ECS-evoked seizures. This demonstrates that
    DNA DSB damage is an especially sensitive indicator of neuronal endangerment
    and that it is responsive to neuroprotective intervention.
    BibTeX:
    @article{Crowe2011,
      author = {Samantha L Crowe and Susanna Tsukerman and Karen Gale and Timothy J Jorgensen and Alexei D Kondratyev},
      title = {Phosphorylation of Histone H2A.X as an Early Marker of Neuronal Endangerment following Seizures in the Adult Rat Brain.},
      journal = {J Neurosci},
      school = {Interdisciplinary Program in Neuroscience and Departments of Pharmacology, Pediatrics, and Radiation Medicine, Georgetown University, Washington, DC 20057.},
      year = {2011},
      volume = {31},
      number = {21},
      pages = {7648--7656},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.0092-11.2011},
      doi = {http://doi.org/10.1523/JNEUROSCI.0092-11.2011}
    }
    
    Dudak, A., Kim, J., Cheong, B., Federoff, H.J. & Lim, S.T. Membrane palmitoylated proteins regulate trafficking and processing of nectins. 2011 Eur J Cell Biol
    Vol. 90(5), pp. 365-375School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd. NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Nectins are cell-cell adhesion molecules involved in the formation
    of various intercellular junctions and the establishment of apical-basal
    polarity at cell-cell adhesion sites. To have a better understanding
    of the roles of nectins in the formation of cell-cell junctions,
    we searched for new cytoplasmic binding partners for nectin. We report
    that nectin-1? associates with membrane palmitoylated protein 3 (MPP3),
    one of the human homologues of a Drosophila tumor suppressor gene,
    Disc large. Two major forms of MPP3 at 66 and 98 kDa were detected,
    in conjunction with nectin-1?, suggesting that an association between
    the two may occur in various cell types. Nectin-1? recruits MPP3
    to cell-cell contact sites, mediated by a PDZ-binding motif at the
    carboxyl terminus of nectin-1?. Association with MPP3 increases cell
    surface expression of nectin-1? and enhances nectin-1? ectodomain
    shedding, indicating that MPP3 regulates trafficking and processing
    of nectin-1?. Further study showed that MPP3 interacts with nectin-3?,
    but not with nectin-2?, showing that the association of nectins with
    MPP3 is isoform-specific. MPP5, another MPP family member, interacts
    with nectins with varying affinity and facilitates surface expression
    of nectin-1?, nectin-2?, and nectin-3?. These data suggest that wide
    interactions between nectins and MPP family members may occur in
    various cell-cell junctions and that these associations may regulate
    trafficking and processing of nectins.
    BibTeX:
    @article{Dudak2011,
      author = {Amanda Dudak and Jinsook Kim and Bryan Cheong and Howard J Federoff and Seung T Lim},
      title = {Membrane palmitoylated proteins regulate trafficking and processing of nectins.},
      journal = {Eur J Cell Biol},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd. NW, Washington, DC 20057, USA.},
      year = {2011},
      volume = {90},
      number = {5},
      pages = {365--375},
      url = {http://dx.doi.org/10.1016/j.ejcb.2011.01.004},
      doi = {http://doi.org/10.1016/j.ejcb.2011.01.004}
    }
    
    Dumanis, S.B., Cha, H.-J., Song, J.M., Trotter, J.H., Spitzer, M., Lee, J.-Y., Weeber, E.J., Turner, R.S., Pak, D.T.S., Rebeck, G.W. & Hoe, H.-S. ApoE receptor 2 regulates synapse and dendritic spine formation. 2011 PLoS One
    Vol. 6(2), pp. e17203School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America. 
    DOI URL 
    Abstract: Apolipoprotein E receptor 2 (ApoEr2) is a postsynaptic protein involved
    in long-term potentiation (LTP), learning, and memory through unknown
    mechanisms. We examined the biological effects of ApoEr2 on synapse
    and dendritic spine formation-processes critical for learning and
    memory.In a heterologous co-culture synapse assay, overexpression
    of ApoEr2 in COS7 cells significantly increased colocalization with
    synaptophysin in primary hippocampal neurons, suggesting that ApoEr2
    promotes interaction with presynaptic structures. In primary neuronal
    cultures, overexpression of ApoEr2 increased dendritic spine density.
    Consistent with our in vitro findings, ApoEr2 knockout mice had decreased
    dendritic spine density in cortical layers II/III at 1 month of age.
    We also tested whether the interaction between ApoEr2 and its cytoplasmic
    adaptor proteins, specifically X11? and PSD-95, affected synapse
    and dendritic spine formation. X11? decreased cell surface levels
    of ApoEr2 along with synapse and dendritic spine density. In contrast,
    PSD-95 increased cell surface levels of ApoEr2 as well as synapse
    and dendritic spine density.These results suggest that ApoEr2 plays
    important roles in structure and function of CNS synapses and dendritic
    spines, and that these roles are modulated by cytoplasmic adaptor
    proteins X11? and PSD-95.
    BibTeX:
    @article{Dumanis2011,
      author = {Sonya B Dumanis and Hyun-Jung Cha and Jung Min Song and Justin H Trotter and Matthew Spitzer and Ji-Yun Lee and Edwin J Weeber and R. Scott Turner and Daniel T S Pak and G. William Rebeck and Hyang-Sook Hoe},
      title = {ApoE receptor 2 regulates synapse and dendritic spine formation.},
      journal = {PLoS One},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United States of America.},
      year = {2011},
      volume = {6},
      number = {2},
      pages = {e17203},
      url = {http://dx.doi.org/10.1371/journal.pone.0017203},
      doi = {http://doi.org/10.1371/journal.pone.0017203}
    }
    
    Feng, L.R. & Maguire-Zeiss, K.A. Dopamine and paraquat enhance α-synuclein-induced alterations in membrane conductance. 2011 Neurotox Res
    Vol. 20(4), pp. 387-401School: Department of Neuroscience and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: We have previously demonstrated that α-synuclein overexpression increases
    the membrane conductance of dopaminergic-like cells. Although α-synuclein
    is thought to play a central role in the pathogenesis of several
    neurodegenerative diseases including Parkinson's disease, multiple
    system atrophy, and diffuse Lewy body disease, the mechanism of action
    is not completely understood. In this study, we sought to determine
    whether multiple factors act together with α-synuclein to engender
    cell vulnerability through an augmentation of membrane conductance.
    In this article, we employed a cell model that mimics dopaminergic
    neurons coupled with α-synuclein overexpression and oxidative stressors.
    We demonstrate an enhancement of α-synuclein-induced toxicity in
    the presence of combined treatment with dopamine and paraquat, two
    molecules known to incite oxidative stress. In addition, we show
    that combined dopamine and paraquat treatment increases the expression
    of heme oxygenase-1, an antioxidant response protein. Finally, we
    demonstrate for the first time that combined treatment of dopaminergic
    cells with paraquat and dopamine enhances α-synuclein-induced leak
    channel properties resulting in increased membrane conductance. Importantly,
    these increases are most robust when both paraquat and dopamine are
    present suggesting the need for multiple oxidative insults to augment
    α-synuclein-induced disruption of membrane integrity.
    BibTeX:
    @article{Feng2011,
      author = {Feng, Li Rebekah and Maguire-Zeiss, Kathleen A.},
      title = {Dopamine and paraquat enhance α-synuclein-induced alterations in membrane conductance.},
      journal = {Neurotox Res},
      school = {Department of Neuroscience and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd NW, Washington, DC 20057, USA.},
      year = {2011},
      volume = {20},
      number = {4},
      pages = {387--401},
      url = {http://dx.doi.org/10.1007/s12640-011-9255-x},
      doi = {http://doi.org/10.1007/s12640-011-9255-x}
    }
    
    Forcelli, P.A., Gale, K. & Kondratyev, A. Early postnatal exposure of rats to lamotrigine, but not phenytoin, reduces seizure threshold in adulthood. 2011 Epilepsia
    Vol. 52(4), pp. e20-e22School: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: In view of previous reports of changes in seizure susceptibility in
    adult rats exposed to phenobarbital or diazepam as pups, we examined
    the effects of early life exposure to lamotrigine and phenytoin,
    two commonly used antiepileptic drugs (AEDs), for their effect on
    seizure threshold in adult rats. We found that pups exposed to lamotrigine
    for 6 days during the second postnatal week had a significantly lower
    threshold for pentylenetetrazole-evoked seizures when tested as adults.
    In contrast, phenytoin exposure during the second postnatal week
    was without a significant effect on seizure threshold in adults.
    Seizure scores at threshold were comparable across all groups tested.
    The dose of lamotrigine used in our study (20 mg/kg) was below that
    required to cause developmental neuronal apoptosis, whereas the dose
    of phenytoin used (50 mg/kg) was above that required for developmental
    neurotoxicity. Therefore, our findings suggest that neurodevelopmental
    alterations in seizure susceptibility may occur via mechanisms that
    are independent of those responsible for neural injury or teratogenesis.
    Our findings support the possibility that therapy with certain AEDs
    during pregnancy or infancy may alter seizure susceptibility later
    in life, a possibility that should be taken into account when examining
    early life factors that contribute to seizure susceptibility in adulthood.
    BibTeX:
    @article{Forcelli2011,
      author = {Patrick A Forcelli and Karen Gale and Alexei Kondratyev},
      title = {Early postnatal exposure of rats to lamotrigine, but not phenytoin, reduces seizure threshold in adulthood.},
      journal = {Epilepsia},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA.},
      year = {2011},
      volume = {52},
      number = {4},
      pages = {e20--e22},
      url = {http://dx.doi.org/10.1111/j.1528-1167.2010.02971.x},
      doi = {http://doi.org/10.1111/j.1528-1167.2010.02971.x}
    }
    
    Forcelli, P.A., Kim, J., Kondratyev, A. & Gale, K. Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain. 2011 Epilepsia
    Vol. 52(12), pp. e207-e211School: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA. paf22@georgetown.edu 
    DOI URL 
    Abstract: The induction of neuronal apoptosis throughout many regions of the
    developing rat brain by phenobarbital and phenytoin, two drugs commonly
    used for the treatment of neonatal seizures, has been well documented.
    However, several limbic regions have not been included in previous
    analyses. Because drug-induced damage to limbic brain regions in
    infancy could contribute to emotional and psychiatric sequelae, it
    is critical to determine the extent to which these regions are vulnerable
    to developmental neurotoxicity. To evaluate the impact of antiepileptic
    drug (AED) exposure on limbic nuclei, we treated postnatal day 7
    rat pups with phenobarbital, phenytoin, carbamazepine, or vehicle,
    and examined nucleus accumbens, septum, amygdala, piriform cortex,
    and frontal cortex for cell death. Histologic sections were processed
    using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end
    labeling (TUNEL) assay to label apoptotic cells. Nucleus accumbens
    displayed the highest level of baseline cell death (vehicle group),
    as well as the greatest net increase in cell death following phenobarbital
    or phenytoin. Phenobarbital exposure resulted in a significant increase
    in cell death in all brain regions, whereas phenytoin exposure increased
    cell death only in the nucleus accumbens. Carbamazepine was without
    effect on cell death in any brain region analyzed, suggesting that
    the neurotoxicity observed is not an inherent feature of AED action.
    Our findings demonstrate pronounced cell death in several important
    regions of the rat limbic system following neonatal administration
    of phenobarbital, the first-line treatment for neonatal seizures
    in humans. These findings raise the possibility that AED exposure
    in infancy may contribute to adverse neuropsychiatric outcomes later
    in life.
    BibTeX:
    @article{Forcelli2011a,
      author = {Forcelli, Patrick A. and Kim, Jinsook and Kondratyev, Alexei and Gale, Karen},
      title = {Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain.},
      journal = {Epilepsia},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, District of Columbia, USA. paf22@georgetown.edu},
      year = {2011},
      volume = {52},
      number = {12},
      pages = {e207--e211},
      url = {http://dx.doi.org/10.1111/j.1528-1167.2011.03297.x},
      doi = {http://doi.org/10.1111/j.1528-1167.2011.03297.x}
    }
    
    Gonzalez-Sulser, A., Wang, J., Motamedi, G.K., Avoli, M., Vicini, S. & Dzakpasu, R. The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array. 2011 Neuropharmacology
    Vol. 60(7-8), pp. 1142-1153School: Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA. 
    DOI URL 
    Abstract: Epileptiform discharges recorded in the 4-aminopyridine (4-AP) in
    vitro epilepsy model are mediated by glutamatergic and GABAergic
    signaling. Using a 60-channel perforated multi-electrode array (pMEA)
    on corticohippocampal slices from 2 to 3 week old mice we recorded
    interictal- and ictal-like events. When glutamatergic transmission
    was blocked, interictal-like events no longer initiated in the hilus
    or CA3/CA1 pyramidal layers but originated from the dentate gyrus
    granule and molecular layers. Furthermore, frequencies of interictal-like
    events were reduced and durations were increased in these regions
    while cortical discharges were completely blocked. Following GABA(A)
    receptor blockade interictal-like events no longer propagated to
    the dentate gyrus while their frequency in CA3 increased; in addition,
    ictal-like cortical events became shorter while increasing in frequency.
    Lastly, drugs that affect tonic and synaptic GABAergic conductance
    modulated the frequency, duration, initiation and propagation of
    interictal-like events. These findings confirm and expand on previous
    studies indicating that multiple synaptic mechanisms contribute to
    synchronize neuronal network activity in forebrain structures. This
    article is part of a Special Issue entitled 'Trends in neuropharmacology:
    in memory of Erminio Costa'.
    BibTeX:
    @article{Gonzalez-Sulser2011,
      author = {Alfredo Gonzalez-Sulser and Jing Wang and Gholam K Motamedi and Massimo Avoli and Stefano Vicini and Rhonda Dzakpasu},
      title = {The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array.},
      journal = {Neuropharmacology},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, USA.},
      year = {2011},
      volume = {60},
      number = {7-8},
      pages = {1142--1153},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2010.10.007},
      doi = {http://doi.org/10.1016/j.neuropharm.2010.10.007}
    }
    
    Gordon, E.M., Lee, P.S., Maisog, J.M., Foss-Feig, J., Billington, M.E., Vanmeter, J. & Vaidya, C.J. Strength of default mode resting-state connectivity relates to white matter integrity in children. 2011 Dev Sci
    Vol. 14(4), pp. 738-751School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, USA ?Department of Psychology, Georgetown University, USA ?Department of Pediatrics, Georgetown University Medical Center, USA ?Department of Neurology, Georgetown University Medical Center, USA ?Children's Research Institute, Children's National Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: A default mode network of brain regions is known to demonstrate coordinated
    activity during the resting state. While the default mode network
    is well characterized in adults, few investigations have focused
    upon its development. We scanned 9-13-year-old children with diffusion
    tensor imaging and resting-state functional magnetic resonance imaging.
    We identified resting-state networks using Independent Component
    Analysis and tested whether the functional connectivity between the
    medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC)
    depends upon the maturation of the underlying cingulum white matter
    tract. To determine the generalizability of this relationship, we
    also tested whether functional connectivity depends on white matter
    maturity between bilateral lateral prefrontal cortex (lateral PFC)
    within the executive control network. We found a positive relationship
    between mPFC-PCC connectivity and fractional anisotropy of the cingulum
    bundle; this positive relationship was moderated by the age of the
    subjects such that it was stronger in older children. By contrast,
    no such structure-function relationship emerged between right and
    left lateral PFC. However, functional and structural connectivity
    of this tract related positively with cognitive speed, fluency, and
    set-switching neuropsychological measures.
    BibTeX:
    @article{Gordon2011,
      author = {Evan M Gordon and Philip S Lee and Jose M Maisog and Jennifer Foss-Feig and Michael E Billington and John Vanmeter and Chandan J Vaidya},
      title = {Strength of default mode resting-state connectivity relates to white matter integrity in children.},
      journal = {Dev Sci},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, USA ?Department of Psychology, Georgetown University, USA ?Department of Pediatrics, Georgetown University Medical Center, USA ?Department of Neurology, Georgetown University Medical Center, USA ?Children's Research Institute, Children's National Medical Center, Washington, DC, USA.},
      year = {2011},
      volume = {14},
      number = {4},
      pages = {738--751},
      url = {http://dx.doi.org/10.1111/j.1467-7687.2010.01020.x},
      doi = {http://doi.org/10.1111/j.1467-7687.2010.01020.x}
    }
    
    Gordon, E.M., Stollstorff, M., Devaney, J.M., Bean, S. & Vaidya, C.J. Effect of Dopamine Transporter Genotype on Intrinsic Functional Connectivity Depends on Cognitive State. 2011 Cereb CortexSchool: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.  DOI URL 
    Abstract: Functional connectivity between brain regions can define large-scale
    neural networks and provide information about relationships between
    those networks. We examined how relationships within and across intrinsic
    connectivity networks were 1) sensitive to individual differences
    in dopaminergic function, 2) modulated by cognitive state, and 3)
    associated with executive behavioral traits. We found that regardless
    of cognitive state, connections between frontal, parietal, and striatal
    nodes of Task-Positive networks (TPNs) and Task-Negative networks
    (TNNs) showed higher functional connectivity in 10/10 homozygotes
    of the dopamine transporter gene, a polymorphism influencing synaptic
    dopamine, than in 9/10 heterozygotes. However, performance of a working
    memory task (a state requiring dopamine release) modulated genotype
    differences selectively, such that cross-network connectivity between
    TPNs and TNNs was higher in 10/10 than 9/10 subjects during working
    memory but not during rest. This increased cross-network connectivity
    was associated with increased self-reported measures of impulsivity
    and inattention traits. By linking a gene regulating synaptic dopamine
    to a phenotype characterized by inefficient executive function, these
    findings validate cross-network connectivity as an endophenotype
    of executive dysfunction.
    BibTeX:
    @article{Gordon2011a,
      author = {Gordon, Evan M. and Stollstorff, Melanie and Devaney, Joseph M. and Bean, Stephanie and Vaidya, Chandan J.},
      title = {Effect of Dopamine Transporter Genotype on Intrinsic Functional Connectivity Depends on Cognitive State.},
      journal = {Cereb Cortex},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2011},
      url = {http://dx.doi.org/10.1093/cercor/bhr305},
      doi = {http://doi.org/10.1093/cercor/bhr305}
    }
    
    Gordon, E.M., Stollstorff, M. & Vaidya, C.J. Using spatial multiple regression to identify intrinsic connectivity networks involved in working memory performance. 2011 Hum Brain MappSchool: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. emg56@georgetown.edu.  DOI URL 
    Abstract: Many researchers have noted that the functional architecture of the
    human brain is relatively invariant during task performance and the
    resting state. Indeed, intrinsic connectivity networks (ICNs) revealed
    by resting-state functional connectivity analyses are spatially similar
    to regions activated during cognitive tasks. This suggests that patterns
    of task-related activation in individual subjects may result from
    the engagement of one or more of these ICNs; however, this has not
    been tested. We used a novel analysis, spatial multiple regression,
    to test whether the patterns of activation during an N-back working
    memory task could be well described by a linear combination of ICNs
    delineated using Independent Components Analysis at rest. We found
    that across subjects, the cingulo-opercular Set Maintenance ICN,
    as well as right and left Frontoparietal Control ICNs, were reliably
    activated during working memory, while Default Mode and Visual ICNs
    were reliably deactivated. Further, involvement of Set Maintenance,
    Frontoparietal Control, and Dorsal Attention ICNs was sensitive to
    varying working memory load. Finally, the degree of left Frontoparietal
    Control network activation predicted response speed, while activation
    in both left Frontoparietal Control and Dorsal Attention networks
    predicted task accuracy. These results suggest that a close relationship
    between resting-state networks and task-evoked activation is functionally
    relevant for behavior, and that spatial multiple regression analysis
    is a suitable method for revealing that relationship. Hum Brain Mapp,
    2011. © 2011 Wiley-Liss, Inc.
    BibTeX:
    @article{Gordon2011b,
      author = {Gordon, Evan M. and Stollstorff, Melanie and Vaidya, Chandan J.},
      title = {Using spatial multiple regression to identify intrinsic connectivity networks involved in working memory performance.},
      journal = {Hum Brain Mapp},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. emg56@georgetown.edu.},
      year = {2011},
      url = {http://dx.doi.org/10.1002/hbm.21306},
      doi = {http://doi.org/10.1002/hbm.21306}
    }
    
    Herman, A.M. & Moussa, C.E.-H. The ubiquitin ligase parkin modulates the execution of autophagy. 2011 Autophagy
    Vol. 7(8)School: Department of Neuroscience; Georgetown University Medical Center; Washington D.C. USA. 
     
    BibTeX:
    @article{Herman2011,
      author = {Alexander M Herman and Charbel E-H Moussa},
      title = {The ubiquitin ligase parkin modulates the execution of autophagy.},
      journal = {Autophagy},
      school = {Department of Neuroscience; Georgetown University Medical Center; Washington D.C. USA.},
      year = {2011},
      volume = {7},
      number = {8}
    }
    
    Khandelwal, P.J., Herman, A.M., Hoe, H.-S., Rebeck, G.W. & Moussa, C.E.-H. Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Abeta in AD models. 2011 Hum Mol Genet
    Vol. 20(11), pp. 2091-2102School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Intraneuronal amyloid-β (AΒ) may contribute to extracellular plaque
    deposition, the characteristic pathology of Alzheimer's disease (AD).
    The E3-ubiquitin ligase parkin ubiquitinates intracellular proteins
    and induces mitophagy. We previously demonstrated that parkin reduces
    AΒ levels in lentiviral models of intracellular AΒ. Here we used
    a triple transgenic AD (3xTg-AD) mouse, which over-expresses APP(Swe),
    Tau(P301L) and harbor the PS1(M146V) knock-in mutation and found
    that lentiviral parkin ubiquitinated intracellular AΒ in vivo, stimulated
    beclin-dependent molecular cascade of autophagy and facilitated clearance
    of vesicles containing debris and defective mitochondria. Parkin
    expression decreased intracellular AΒ levels and extracellular plaque
    deposition. Parkin expression also attenuated caspase activity, prevented
    mitochondrial dysfunction and oxidative stress and restored neurotransmitter
    synthesis. Restoration of glutamate synthesis, which was independent
    of glial-neuronal recycling, depended on mitochondrial activity and
    led to an increase in ?-amino butyric acid levels. These data indicate
    that parkin may be used as an alternative strategy to reduce AΒ levels
    and enhance autophagic clearance of AΒ-induced defects in AD. Parkin-mediated
    clearance of ubiquitinated AΒ may act in parallel with autophagy
    to clear molecular debris and defective mitochondria and restore
    neurotransmitter balance.
    BibTeX:
    @article{Khandelwal2011a,
      author = {Khandelwal, Preeti J. and Herman, Alexander M. and Hoe, Hyang-Sook and Rebeck, G William and Moussa, Charbel E-H.},
      title = {Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Abeta in AD models.},
      journal = {Hum Mol Genet},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2011},
      volume = {20},
      number = {11},
      pages = {2091--2102},
      url = {http://dx.doi.org/10.1093/hmg/ddr091},
      doi = {http://doi.org/10.1093/hmg/ddr091}
    }
    
    Khandelwal, P.J., Herman, A.M. & Moussa, C.E.-H. Inflammation in the early stages of neurodegenerative pathology. 2011 J Neuroimmunol
    Vol. 238(1-2), pp. 1-11School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Inflammation is secondary to protein accumulation in neurodegenerative
    diseases, including Alzheimer's, Parkinson's and Amyotrophic Lateral
    Sclerosis. Emerging evidence indicate sustained inflammatory responses,
    involving microglia and astrocytes in animal models of neurodegeneration.
    It is unknown whether inflammation is beneficial or detrimental to
    disease progression and how inflammatory responses are induced within
    the CNS. Persistence of an inflammatory stimulus or failure to resolve
    sustained inflammation can result in pathology, thus, mechanisms
    that counteract inflammation are indispensable. Here we review studies
    on inflammation mediated by innate and adaptive immunity in the early
    stages of neurodegeneration and highlight important areas for future
    investigation.
    BibTeX:
    @article{Khandelwal2011,
      author = {Khandelwal, Preeti J. and Herman, Alexander M. and Moussa, Charbel E-H.},
      title = {Inflammation in the early stages of neurodegenerative pathology.},
      journal = {J Neuroimmunol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2011},
      volume = {238},
      number = {1-2},
      pages = {1--11},
      url = {http://dx.doi.org/10.1016/j.jneuroim.2011.07.002},
      doi = {http://doi.org/10.1016/j.jneuroim.2011.07.002}
    }
    
    Kim, J., Chang, A., Dudak, A., Federoff, H.J. & Lim, S.T. Characterization of nectin processing mediated by presenilin-dependent gamma-secretase. 2011 J Neurochem
    Vol. 119(5), pp. 945-956School: Department of Neuroscience, Georgetown University Medical Center, NW, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: Nectins play an important role in forming various intercellular junctions
    including synapses. This role is regulated by several secretases
    present at intercellular junctions. We have investigated presenilin
    (PS)-dependent secretase-mediated processing of nectins in PS1 KO
    cells and primary hippocampal neurons. The loss of PS1/gamma-secretase
    activity delayed the processing of nectin-1 and caused the accumulation
    of its full-length and C-terminal fragments. Over-expression of PS2
    in PS1 KO cells compensated for the loss of PS1, suggesting that
    PS2 also has the ability to regulate nectin-1 processing. In mouse
    brain slices, a pronounced increase in levels of 30 and 24 kDa C-terminal
    fragments in response to chemical long-term potentiation was observed.
    The mouse brain synaptosomal fractionation study indicated that nectin-1
    localized to post-synaptic and preferentially pre-synaptic membranes
    and that shedding occurs in both compartments. These data suggest
    that nectin-1 shedding and PS-dependent intramembrane cleavage occur
    at synapses, and is a regulated event during conditions of synaptic
    plasticity in the brain. Point mutation analysis identified several
    residues within the transmembrane domain that play a critical role
    in the positioning of cleavage sites by ectodomain sheddases. Nectin-3,
    which forms hetero-trans-dimers with nectin-1, also undergoes intramembrane
    cleavage mediated by PS1/gamma-secretase, suggesting that PS1/gamma-secretase
    activity regulates synapse formation and remodeling by nectin processing.
    BibTeX:
    @article{Kim2011,
      author = {Kim, Jinsook and Chang, Allison and Dudak, Amanda and Federoff, Howard J. and Lim, Seung T.},
      title = {Characterization of nectin processing mediated by presenilin-dependent gamma-secretase.},
      journal = {J Neurochem},
      school = {Department of Neuroscience, Georgetown University Medical Center, NW, Washington, District of Columbia, USA.},
      year = {2011},
      volume = {119},
      number = {5},
      pages = {945--956},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07479.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2011.07479.x}
    }
    
    Krafnick, A.J., Flowers, D.L., Napoliello, E.M. & Eden, G.F. Gray matter volume changes following reading intervention in dyslexic children. 2011 Neuroimage
    Vol. 57(3), pp. 733-741School: Center for the Study of Learning, Georgetown University Medical Center, 4000 Reservoir Road, Building D Suite 150, Washington, DC 20057, USA. ajk53@georgetown.edu 
    DOI URL 
    Abstract: Studies in children and adults with the reading disability developmental
    dyslexia have shown behavioral improvements after reading intervention.
    In another line of work, it has been shown that intensive training
    in a variety of cognitive and sensorimotor skills can result in changes
    in gray matter volume (GMV). This study examined changes in GMV following
    intensive reading intervention in children with dyslexia using voxel-based
    morphometry (VBM). Eleven dyslexic children underwent an eight week
    training focused on mental imagery, articulation and tracing of letters,
    groups of letters and words, which resulted in significant gains
    in reading skills. This was followed by an eight week null period
    (control) where no intervention was administered and no further significant
    gains in reading were observed. Structural scans were obtained before
    the intervention, after the intervention and after the null period.
    GMV increases between the first two time points were found in the
    left anterior fusiform gyrus/hippocampus, left precuneus, right hippocampus
    and right anterior cerebellum. However these areas did not change
    between time points two and three (control period), suggesting that
    the changes were specific to the intervention period. These results
    demonstrate for the first time that (1) training-induced changes
    in GMV can be observed in a pediatric sample and (2) reading improvements
    induced by intervention are accompanied by GMV changes.
    BibTeX:
    @article{Krafnick2011,
      author = {Krafnick, Anthony J. and Flowers, D Lynn and Napoliello, Eileen M. and Eden, Guinevere F.},
      title = {Gray matter volume changes following reading intervention in dyslexic children.},
      journal = {Neuroimage},
      school = {Center for the Study of Learning, Georgetown University Medical Center, 4000 Reservoir Road, Building D Suite 150, Washington, DC 20057, USA. ajk53@georgetown.edu},
      year = {2011},
      volume = {57},
      number = {3},
      pages = {733--741},
      url = {http://dx.doi.org/10.1016/j.neuroimage.2010.10.062},
      doi = {http://doi.org/10.1016/j.neuroimage.2010.10.062}
    }
    
    Lim, S.T., Esfahani, K., Avdoshina, V. & Mocchetti, I. Exogenous gangliosides increase the release of brain-derived neurotrophic factor. 2011 Neuropharmacology
    Vol. 60(7-8), pp. 1160-1167School: Department of Neuroscience, Georgetown University Medical Center, New Research Building EP-04, 3970 Reservoir Rd, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Gangliosides are lipophilic compounds found in cell plasma membranes
    throughout the brain that play a role in neuronal plasticity and
    regeneration. Indeed, absence or abnormal accumulation of gangliosides
    has been shown to lead to neurological disorders. Experimental data
    have shown that exogenous gangliosides exhibit properties similar
    to the neurotrophins, a family of neurotrophic factors that are important
    in the survival and maintenance of neurons and prevention of neurological
    diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant
    of the neurotrophins. This work was done to reveal the neurotrophic
    mechanism of exogenous gangliosides. In particular, we examined whether
    gangliosides promote the release of BDNF. Rat hippocampal neurons
    or human neuroblastoma cells were transduced with a recombinant adenovirus
    expressing BDNF-flag to facilitate detection of BDNF. Release of
    BDNF was then determined by Western blot analysis and a two-site
    immunoassay of culture medium. The depolarizing agent KCl was used
    as a comparison. In hippocampal neurons, both GM1 ganglioside and
    KCl evoked within minutes the release of mature BDNF. In human cells,
    GM1 and other gangliosides released both mature BDNF and pro-BDNF.
    The effect of gangliosides was structure-dependent. In fact, GT1b
    preferentially released mature BDNF whereas GM1 released both mature
    and pro-BDNF. Ceramide and sphingosine did not modify the release
    of BDNF. This work provides additional experimental evidence that
    exogenous gangliosides can be used to enhance the neurotrophic factor
    environment and promote neuronal survival in neurological diseases.
    This article is part of a Special Issue entitled 'Trends in neuropharmacology:
    in memory of Erminio Costa'.
    BibTeX:
    @article{Lim2011,
      author = {Seung T Lim and Kamilla Esfahani and Valeriya Avdoshina and Italo Mocchetti},
      title = {Exogenous gangliosides increase the release of brain-derived neurotrophic factor.},
      journal = {Neuropharmacology},
      school = {Department of Neuroscience, Georgetown University Medical Center, New Research Building EP-04, 3970 Reservoir Rd, Washington, DC 20057, USA.},
      year = {2011},
      volume = {60},
      number = {7-8},
      pages = {1160--1167},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2010.10.012},
      doi = {http://doi.org/10.1016/j.neuropharm.2010.10.012}
    }
    
    Loane, D.J., Washington, P.M., Vardanian, L., Pocivavsek, A., Hoe, H.-S., Duff, K.E., Cernak, I., Rebeck, G.W., Faden, A.I. & Burns, M.P. Modulation of ABCA1 by an LXR agonist reduces beta-amyloid levels and improves outcome after traumatic brain injury. 2011 J Neurotrauma
    Vol. 28(2), pp. 225-236School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Traumatic brain injury (TBI) increases brain beta-amyloid (AΒ) in
    humans and animals. Although the role of AΒ in the injury cascade
    is unknown, multiple preclinical studies have demonstrated a correlation
    between reduced AΒ and improved outcome. Therefore, therapeutic strategies
    that enhance AΒ clearance may be beneficial after TBI. Increased
    levels of ATP-binding cassette A1 (ABCA1) transporters can enhance
    AΒ clearance through an apolipoprotein E (apoE)-mediated pathway.
    By measuring AΒ and ABCA1 after experimental TBI in C57BL/6J mice,
    we found that AΒ peaked early after injury (1-3 days), whereas ABCA1
    had a delayed response (beginning at 3 days). As ABCA1 levels increased,
    AΒ levels returned to baseline levels-consistent with the known role
    of ABCA1 in AΒ clearance. To test if enhancing ABCA1 levels could
    block TBI-induced AΒ, we treated TBI mice with the liver X-receptor
    (LXR) agonist T0901317. Pre- and post-injury treatment increased
    ABCA1 levels at 24h post-injury, and reduced the TBI-induced increase
    in AΒ. This reduction in AΒ was not due to decreased amyloid precursor
    protein processing, or a shift in the solubility of AΒ, indicating
    enhanced clearance. T0901317 also limited motor coordination deficits
    in injured mice and reduced brain lesion volume. These data indicate
    that activation of LXR can reduce AΒ accumulation after TBI, and
    is accompanied by improved functional recovery.
    BibTeX:
    @article{Loane2011,
      author = {David J Loane and Patricia M Washington and Lilit Vardanian and Ana Pocivavsek and Hyang-Sook Hoe and Karen E Duff and Ibolja Cernak and G. William Rebeck and Alan I Faden and Mark P Burns},
      title = {Modulation of ABCA1 by an LXR agonist reduces beta-amyloid levels and improves outcome after traumatic brain injury.},
      journal = {J Neurotrauma},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2011},
      volume = {28},
      number = {2},
      pages = {225--236},
      url = {http://dx.doi.org/10.1089/neu.2010.1595},
      doi = {http://doi.org/10.1089/neu.2010.1595}
    }
    
    Malkova, L., Kozikowski, A.P. & Gale, K. The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques. 2011 Neuropharmacology
    Vol. 60(7-8), pp. 1262-1268School: Department of Pharmacology and the Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3900 Reservoir Rd. NW, Washington, DC 20007, USA. malkoval@georgetown.edu 
    DOI URL 
    Abstract: Nootropic agents or cognitive enhancers are purported to improve mental
    functions such as cognition, memory, or attention. The aim of our
    study was to determine the effects of two possible cognitive enhancers,
    huperzine A and IDRA 21, in normal young adult monkeys performing
    a visual memory task of varying degrees of difficulty. Huperzine
    A is a reversible acetylcholinesterase (AChE) inhibitor, its administration
    results in regionally specific increases in acetylcholine levels
    in the brain. In human clinical trials, Huperzine A resulted in cognitive
    improvement in patients with mild to moderate form of Alzheimer's
    disease (AD) showing its potential as a palliative agent in the treatment
    of AD. IDRA 21 is a positive allosteric modulator of glutamate AMPA
    receptors. It increases excitatory synaptic strength by attenuating
    rapid desensitization of AMPA receptors and may thus have beneficial
    therapeutic effects to ameliorate memory deficits in patients with
    cognitive impairments, including AD. The present study evaluated
    the effects of the two drugs in normal, intact, young adult monkeys
    to determine whether they can result in cognitive enhancement in
    a system that is presumably functioning optimally. Six young pigtail
    macaques (Macaca nemestrina) were trained on delayed non-matching-to-sample
    task, a measure of visual recognition memory, up to criterion of
    90% correct responses on each of the four delays (10s, 30s, 60s,
    and 90s). They were then tested on two versions of the task: Task
    1 included the four delays intermixed within a session and the monkeys
    performed it with the accuracy of 90 Task 2 included, in each
    of 24 trials, a list of six objects presented in succession. Two
    objects from the list were then presented for choice paired with
    novel objects and following two of the four delays intermixed within
    a session. This task with a higher mnemonic demand yielded an average
    performance of 64% correct. Oral administration of huperzine A did
    not significantly affect the monkeys' performance on either task.
    However, a significant negative correlation was found between the
    baseline performance on each delay and the change in performance
    under huperzine A, suggesting that under conditions in which the
    subjects were performing poorly (55-69, the drug resulted in improved
    performance, whereas no improvement was obtained when the baseline
    was close to 90 In fact, when the subjects were performing very
    well, huperzine A tended to reduce the performance accuracy, indicating
    that in a system that functions optimally, the increased availability
    of acetylcholine does not improve performance or memory, especially
    when the animals are close to the maximum performance. In contrast,
    oral administration of IDRA 21 significantly improved performance
    on Task 2, especially on the longest delay. This finding supports
    the potential use of this drug in treatment of cognitive and memory
    disorders. This article is part of a Special Issue entitled 'Trends
    in neuropharmacology: in memory of Erminio Costa'.
    BibTeX:
    @article{Malkova2011,
      author = {Ludise Malkova and Alan P Kozikowski and Karen Gale},
      title = {The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques.},
      journal = {Neuropharmacology},
      school = {Department of Pharmacology and the Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, 3900 Reservoir Rd. NW, Washington, DC 20007, USA. malkoval@georgetown.edu},
      year = {2011},
      volume = {60},
      number = {7-8},
      pages = {1262--1268},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2010.12.018},
      doi = {http://doi.org/10.1016/j.neuropharm.2010.12.018}
    }
    
    Minami, S.S., Hoe, H.-S. & Rebeck, G.W. Fyn kinase regulates the association between amyloid precursor protein and Dab1 by promoting their localization to detergent-resistant membranes. 2011 J NeurochemSchool: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA Department of Neurology, Georgetown University Medical Center, Washington, District of Columbia, USA.  DOI URL 
    Abstract: J. Neurochem. (2011) 10.1111/j.1471-4159.2011.07296.x ABSTRACT: The
    adaptor protein Disabled1 (Dab1) interacts with amyloid precursor
    protein (APP) and decreases its pathological processing, an effect
    mediated by Fyn tyrosine kinase. Fyn is highly enriched in lipid
    rafts, a major site of pathological APP processing. To investigate
    the role of Fyn in the localization and phosphorylation of APP and
    Dab1 in lipid rafts, we isolated detergent-resistant membrane (DRM)
    fractions from wild-type and Fyn knock-out mice. In wild-type mice,
    all of the Fyn kinase, 17% of total APP, and 33% of total Dab1
    were found in DRMs. Nearly all of the tyrosine phosphorylated forms
    of APP and Dab1 were in DRMs. APP and Dab1 co-precipitated both in
    and out of DRM fractions, indicating an association that is independent
    of subcellular localization. Fyn knock-out mice had decreased APP,
    Dab1, and tyrosine-phosphorylated Dab1 in DRMs but increased co-immunoprecipitation
    of DRM APP and Dab1. Expression of phosphorylation deficient APP
    or Dab1 constructs revealed that phosphorylation of APP increases,
    whereas phosphorylation of Dab1 decreases, the interaction between
    APP and Dab1. Consistent with these observations, Reelin treatment
    led to increased Dab1 phosphorylation and decreased association between
    APP and Dab1. Reelin also caused increased localization of APP and
    Dab1 to DRMs, an effect that was not seen in Fyn knock-out neurons.
    These findings suggest that Reelin treatment promotes the localization
    of APP and Dab1 to DRMs, and affects their phosphorylation by Fyn,
    thus regulating their interaction.
    BibTeX:
    @article{Minami2011,
      author = {S. Sakura Minami and Hyang-Sook Hoe and G. William Rebeck},
      title = {Fyn kinase regulates the association between amyloid precursor protein and Dab1 by promoting their localization to detergent-resistant membranes.},
      journal = {J Neurochem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA Department of Neurology, Georgetown University Medical Center, Washington, District of Columbia, USA.},
      year = {2011},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07296.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2011.07296.x}
    }
    
    Minami, S.S., Hoe, H.-S. & Rebeck, G.W. Fyn kinase regulates the association between amyloid precursor protein and Dab1 by promoting their localization to detergent-resistant membranes. 2011 J Neurochem
    Vol. 118(5), pp. 879-890School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20057-1464, USA. 
    DOI URL 
    Abstract: The adaptor protein Disabled1 (Dab1) interacts with amyloid precursor
    protein (APP) and decreases its pathological processing, an effect
    mediated by Fyn tyrosine kinase. Fyn is highly enriched in lipid
    rafts, a major site of pathological APP processing. To investigate
    the role of Fyn in the localization and phosphorylation of APP and
    Dab1 in lipid rafts, we isolated detergent-resistant membrane (DRM)
    fractions from wild-type and Fyn knock-out mice. In wild-type mice,
    all of the Fyn kinase, 17% of total APP, and 33% of total Dab1
    were found in DRMs. Nearly all of the tyrosine phosphorylated forms
    of APP and Dab1 were in DRMs. APP and Dab1 co-precipitated both in
    and out of DRM fractions, indicating an association that is independent
    of subcellular localization. Fyn knock-out mice had decreased APP,
    Dab1, and tyrosine-phosphorylated Dab1 in DRMs but increased co-immunoprecipitation
    of DRM APP and Dab1. Expression of phosphorylation deficient APP
    or Dab1 constructs revealed that phosphorylation of APP increases,
    whereas phosphorylation of Dab1 decreases, the interaction between
    APP and Dab1. Consistent with these observations, Reelin treatment
    led to increased Dab1 phosphorylation and decreased association between
    APP and Dab1. Reelin also caused increased localization of APP and
    Dab1 to DRMs, an effect that was not seen in Fyn knock-out neurons.
    These findings suggest that Reelin treatment promotes the localization
    of APP and Dab1 to DRMs, and affects their phosphorylation by Fyn,
    thus regulating their interaction.
    BibTeX:
    @article{Minami2011a,
      author = {Minami, S Sakura and Hoe, Hyang-Sook and Rebeck, G William},
      title = {Fyn kinase regulates the association between amyloid precursor protein and Dab1 by promoting their localization to detergent-resistant membranes.},
      journal = {J Neurochem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia 20057-1464, USA.},
      year = {2011},
      volume = {118},
      number = {5},
      pages = {879--890},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2011.07296.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2011.07296.x}
    }
    
    Mocchetti, I. Pharmacological regulation of gene expression. 2011 Pharmacol Res
    Vol. 64(4), pp. 323-326School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States. moccheti@georgetown.edu 
    DOI URL 
    Abstract: Pharmacological regulation of gene expression was one of the top professional
    interests of Dr. Costa. He promoted the idea that drugs can improve
    the endogenous mechanisms of synaptic plasticity by modulating gene
    expression. In this article I reflect upon Dr. Costa's leadership
    in projects undertaken at FGIN that were aimed at elucidating how
    neurotransmitter receptor activation could affect brain function
    by modulating genes and their products. I will be presenting examples
    of how pharmacological tools can change gene expression. These include
    the ability of drugs of abuse to alter the synthesis of opioid peptides
    or an endogenous ligand for GABAA receptor. I will conclude with
    a brief summary of intriguing discoveries about the regulation of
    nerve growth factor (NGF) and its receptors by beta-receptor agonists,
    adrenal steroids and cytokines.
    BibTeX:
    @article{Mocchetti2011,
      author = {Mocchetti, Italo},
      title = {Pharmacological regulation of gene expression.},
      journal = {Pharmacol Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States. moccheti@georgetown.edu},
      year = {2011},
      volume = {64},
      number = {4},
      pages = {323--326},
      url = {http://dx.doi.org/10.1016/j.phrs.2011.05.019},
      doi = {http://doi.org/10.1016/j.phrs.2011.05.019}
    }
    
    Mocchetti, I. & Guidotti, A. The Fidia-Georgetown Institute for the Neurosciences (FGIN) 1985-1994. 2011 Pharmacol Res
    Vol. 64(4), pp. 314-315School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. moccheti@georgetown.edu 
    DOI URL 
    Abstract: This article describes briefly the history and activities of the Fidia-Georgetown
    Institute for the Neurosciences (FGIN), from its establishment in
    1985 to its closure in 1994. It also provides a list of those colleagues
    and students who worked at FGIN and contributed to various research
    projects.
    BibTeX:
    @article{Mocchetti2011a,
      author = {Mocchetti, Italo and Guidotti, Alessandro},
      title = {The Fidia-Georgetown Institute for the Neurosciences (FGIN) 1985-1994.},
      journal = {Pharmacol Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. moccheti@georgetown.edu},
      year = {2011},
      volume = {64},
      number = {4},
      pages = {314--315},
      url = {http://dx.doi.org/10.1016/j.phrs.2011.05.015},
      doi = {http://doi.org/10.1016/j.phrs.2011.05.015}
    }
    
    N'Gouemo, P. Targeting BK (big potassium) channels in epilepsy. 2011 Expert Opin Ther Targets
    Vol. 15(11), pp. 1283-1295School: Georgetown University Medical Center, Interdisciplinary Program in Neuroscience and Department of Pediatrics, Washington, DC 20057, USA. pn@georgetown.edu 
    DOI URL 
    Abstract: INTRODUCTION: Epilepsies are disorders of neuronal excitability characterized
    by spontaneous and recurrent seizures. Ion channels are critical
    for regulating neuronal excitability and, therefore, can contribute
    significantly to epilepsy pathophysiology. In particular, large conductance,
    Ca2+-activated K+ (BKCa) channels play an important role in seizure
    etiology. These channels are activated by both membrane depolarization
    and increased intracellular Ca2+. This unique coupling of Ca2+ signaling
    to membrane depolarization is important in controlling neuronal hyperexcitability,
    as outward K+ current through BKCa channels hyperpolarizes neurons.
    AREAS COVERED: BKCa channel structure-function and the role of these
    channels in epilepsy pathophysiology. EXPERT OPINION: Loss-of-function
    BKCa channel mutations contribute to neuronal hyperexcitability that
    can lead to temporal lobe epilepsy, tonic-clonic seizures and alcohol
    withdrawal seizures. Similarly, BKCa channel blockade can trigger
    seizures and status epilepticus. Paradoxically, some mutations in
    BKCa channel subunit can give rise to channel gain-of-function that
    leads to development of idiopathic epilepsy (primarily absence epilepsy).
    Seizures themselves also enhance BKCa channel currents associated
    with neuronal hyperexcitability, and blocking BKCa channels suppresses
    generalized tonic-clonic seizures. Thus, both loss-of-function and
    gain-of-function BKCa channels might serve as molecular targets for
    drugs to suppress certain seizure phenotypes including temporal lobe
    seizures and absence seizures, respectively.
    BibTeX:
    @article{NGouemo2011,
      author = {N'Gouemo, Prosper},
      title = {Targeting BK (big potassium) channels in epilepsy.},
      journal = {Expert Opin Ther Targets},
      school = {Georgetown University Medical Center, Interdisciplinary Program in Neuroscience and Department of Pediatrics, Washington, DC 20057, USA. pn@georgetown.edu},
      year = {2011},
      volume = {15},
      number = {11},
      pages = {1283--1295},
      url = {http://dx.doi.org/10.1517/14728222.2011.620607},
      doi = {http://doi.org/10.1517/14728222.2011.620607}
    }
    
    Purcell, J.J., Napoliello, E.M. & Eden, G.F. A combined fMRI study of typed spelling and reading. 2011 Neuroimage
    Vol. 55(2), pp. 750-762School: Center for the Study of Learning, Georgetown University, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: In this study we employed a novel technique to examine the neural
    basis of written spelling by having subjects touch-type single words
    on an fMRI compatible QWERTY keyboard. Additionally, in the same
    group of participants we determined if task-related signal changes
    associated with typed spelling were also co-localized with or separate
    from those for reading. Of particular interest were the left inferior
    frontal gyrus, left inferior parietal lobe as well as an area in
    the left occipitotemporal cortex termed the Visual Word Form Area
    (VWFA), each of which have been associated with both spelling and
    reading. Our results revealed that typed spelling was associated
    with a left hemisphere network of regions which included the inferior
    frontal gyrus, intraparietal sulcus, inferior temporal/fusiform gyrus,
    as well as a region in the superior/middle frontal gyrus, near Exner's
    area. A conjunction analysis of activation associated with spelling
    and reading revealed a significant overlap in the left inferior frontal
    gyrus and occipitotemporal cortex. Interestingly, within the occipitotemporal
    cortex just lateral and superior to the VWFA we identified an area
    that was selectively associated with spelling, as revealed by a direct
    comparison of the two tasks. These results demonstrate that typed
    spelling activates a predominantly left hemisphere network, a subset
    of which is functionally relevant to both spelling and reading. Further
    analysis revealed that the left occipitotemporal cortex contains
    regions with both conjoint and dissociable patterns of activation
    for spelling and reading.
    BibTeX:
    @article{Purcell2011a,
      author = {Purcell, Jeremy J. and Napoliello, Eileen M. and Eden, Guinevere F.},
      title = {A combined fMRI study of typed spelling and reading.},
      journal = {Neuroimage},
      school = {Center for the Study of Learning, Georgetown University, Washington, DC 20057, USA.},
      year = {2011},
      volume = {55},
      number = {2},
      pages = {750--762},
      url = {http://dx.doi.org/10.1016/j.neuroimage.2010.11.042},
      doi = {http://doi.org/10.1016/j.neuroimage.2010.11.042}
    }
    
    Purcell, J.J., Turkeltaub, P.E., Eden, G.F. & Rapp, B. Examining the central and peripheral processes of written word production through meta-analysis. 2011 Front Psychol
    Vol. 2, pp. 239School: Department of Pediatrics, Center for the Study of Learning, Georgetown University Washington, DC, USA. 
    DOI URL 
    Abstract: Producing written words requires "central" cognitive processes (such
    as orthographic long-term and working memory) as well as more peripheral
    processes responsible for generating the motor actions needed for
    producing written words in a variety of formats (handwriting, typing,
    etc.). In recent years, various functional neuroimaging studies have
    examined the neural substrates underlying the central and peripheral
    processes of written word production. This study provides the first
    quantitative meta-analysis of these studies by applying activation
    likelihood estimation (ALE) methods (Turkeltaub et al., 2002). For
    alphabet languages, we identified 11 studies (with a total of 17
    experimental contrasts) that had been designed to isolate central
    and/or peripheral processes of word spelling (total number of participants = 146).
    Three ALE meta-analyses were carried out. One involved the complete
    set of 17 contrasts; two others were applied to subsets of contrasts
    to distinguish the neural substrates of central from peripheral processes.
    These analyses identified a network of brain regions reliably associated
    with the central and peripheral processes of word spelling. Among
    the many significant results, is the finding that the regions with
    the greatest correspondence across studies were in the left inferior
    temporal/fusiform gyri and left inferior frontal gyrus. Furthermore,
    although the angular gyrus (AG) has traditionally been identified
    as a key site within the written word production network, none of
    the meta-analyses found it to be a consistent site of activation,
    identifying instead a region just superior/medial to the left AG
    in the left posterior intraparietal sulcus. These meta-analyses and
    the discussion of results provide a valuable foundation upon which
    future studies that examine the neural basis of written word production
    can build.
    BibTeX:
    @article{Purcell2011,
      author = {Purcell, Jeremy J. and Turkeltaub, Peter E. and Eden, Guinevere F. and Rapp, Brenda},
      title = {Examining the central and peripheral processes of written word production through meta-analysis.},
      journal = {Front Psychol},
      school = {Department of Pediatrics, Center for the Study of Learning, Georgetown University Washington, DC, USA.},
      year = {2011},
      volume = {2},
      pages = {239},
      url = {http://dx.doi.org/10.3389/fpsyg.2011.00239},
      doi = {http://doi.org/10.3389/fpsyg.2011.00239}
    }
    
    Rauschecker, J.P. An expanded role for the dorsal auditory pathway in sensorimotor control and integration. 2011 Hear Res
    Vol. 271(1-2), pp. 16-25School: Department of Physiology and Biophysics, Laboratory of Integrative Neuroscience and Cognition, Georgetown University Medical Center, New Research Building, Room WP19, Washington, DC 20057-1460, USA. rauschej@georgetown.edu 
    DOI URL 
    Abstract: The dual-pathway model of auditory cortical processing assumes that
    two largely segregated processing streams originating in the lateral
    belt subserve the two main functions of hearing: identification of
    auditory "objects", including speech; and localization of sounds
    in space (Rauschecker and Tian, 2000). Evidence has accumulated,
    chiefly from work in humans and nonhuman primates, that an antero-ventral
    pathway supports the former function, whereas a postero-dorsal stream
    supports the latter, i.e processing of space and motion-in-space.
    In addition, the postero-dorsal stream has also been postulated to
    subserve some functions of speech and language in humans. A recent
    review (Rauschecker and Scott, 2009) has proposed the possibility
    that both functions of the postero-dorsal pathway can be subsumed
    under the same structural forward model: an efference copy sent from
    prefrontal and premotor cortex provides the basis for "optimal state
    estimation" in the inferior parietal lobe and in sensory areas of
    the posterior auditory cortex. The current article corroborates this
    model by adding and discussing recent evidence.
    BibTeX:
    @article{Rauschecker2011,
      author = {Josef P Rauschecker},
      title = {An expanded role for the dorsal auditory pathway in sensorimotor control and integration.},
      journal = {Hear Res},
      school = {Department of Physiology and Biophysics, Laboratory of Integrative Neuroscience and Cognition, Georgetown University Medical Center, New Research Building, Room WP19, Washington, DC 20057-1460, USA. rauschej@georgetown.edu},
      year = {2011},
      volume = {271},
      number = {1-2},
      pages = {16--25},
      url = {http://dx.doi.org/10.1016/j.heares.2010.09.001},
      doi = {http://doi.org/10.1016/j.heares.2010.09.001}
    }
    
    Reddy, S.S., Connor, T.E., Weeber, E.J. & Rebeck, W. Similarities and differences in structure, expression, and functions of VLDLR and ApoER2. 2011 Mol Neurodegener
    Vol. 6, pp. 30School: Department of Neuroscience; Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC, 20007, USA. gwr2@georgetown.edu. 
    DOI URL 
    Abstract: ABSTRACT: Very Low Density Lipoprotein Receptor (VLDLR) and Apolipoprotein
    E Receptor 2 (ApoER2) are important receptors in the brain for mediating
    the signaling effects of the extracellular matrix protein Reelin,
    affecting neuronal function in development and in the adult brain.
    VLDLR and ApoER2 are members of the low density lipoprotein family,
    which also mediates the effects of numerous other extracellular ligands,
    including apolipoprotein E. Although VLDLR and ApoER2 are highly
    homologous, they differ in a number of ways, including structural
    differences, expression patterns, alternative splicing, and binding
    of extracellular and intracellular proteins. This review aims to
    summarize important aspects of VLDLR and ApoER2 that may account
    for interesting recent findings that highlight the unique functions
    of each receptor.
    BibTeX:
    @article{Reddy2011,
      author = {Sunil S Reddy and Teal E Connor and Edwin J Weeber and William Rebeck},
      title = {Similarities and differences in structure, expression, and functions of VLDLR and ApoER2.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience; Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC, 20007, USA. gwr2@georgetown.edu.},
      year = {2011},
      volume = {6},
      pages = {30},
      url = {http://dx.doi.org/10.1186/1750-1326-6-30},
      doi = {http://doi.org/10.1186/1750-1326-6-30}
    }
    
    Reddy, S.S., Connor, T.E., Weeber, E.J. & Rebeck, W. Similarities and differences in structure, expression, and functions of VLDLR and ApoER2. 2011 Mol Neurodegener
    Vol. 6, pp. 30School: Department of Neuroscience; Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC, 20007, USA. gwr2@georgetown.edu. 
    DOI URL 
    Abstract: Very Low Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E
    Receptor 2 (ApoER2) are important receptors in the brain for mediating
    the signaling effects of the extracellular matrix protein Reelin,
    affecting neuronal function in development and in the adult brain.
    VLDLR and ApoER2 are members of the low density lipoprotein family,
    which also mediates the effects of numerous other extracellular ligands,
    including apolipoprotein E. Although VLDLR and ApoER2 are highly
    homologous, they differ in a number of ways, including structural
    differences, expression patterns, alternative splicing, and binding
    of extracellular and intracellular proteins. This review aims to
    summarize important aspects of VLDLR and ApoER2 that may account
    for interesting recent findings that highlight the unique functions
    of each receptor.
    BibTeX:
    @article{Reddy2011a,
      author = {Reddy, Sunil S. and Connor, Teal E. and Weeber, Edwin J. and Rebeck, William},
      title = {Similarities and differences in structure, expression, and functions of VLDLR and ApoER2.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience; Georgetown University Medical Center, 3970 Reservoir Rd, NW, Washington, DC, 20007, USA. gwr2@georgetown.edu.},
      year = {2011},
      volume = {6},
      pages = {30},
      url = {http://dx.doi.org/10.1186/1750-1326-6-30},
      doi = {http://doi.org/10.1186/1750-1326-6-30}
    }
    
    Schulkin, J. Social allostasis: anticipatory regulation of the internal milieu. 2011 Front Evol Neurosci
    Vol. 2, pp. 111School: Department of Neuroscience, Georgetown University Washington, DC, USA. 
    DOI URL 
    Abstract: Social regulation of the internal milieu is a fundamental behavioral
    adaptation. Cephalic capability is reflected by anticipatory behaviors
    to serve systemic physiological regulation. Homeostatic regulation,
    a dominant perspective, reflects reactive responses; allostatic regulation,
    the physiology of change, emphasizes longer-term anticipatory, and
    feedforward systems. Steroids, such as cortisol, and peptides such
    as corticotrophin releasing hormone are but one example of such anticipatory
    regulatory systems. The concept of "allostasis" is in part to take
    account of anticipatory control amidst diverse forms of adaptation
    underlying this regulatory adaptation that supports social contact
    and the internal milieu.
    BibTeX:
    @article{Schulkin2011,
      author = {Jay Schulkin},
      title = {Social allostasis: anticipatory regulation of the internal milieu.},
      journal = {Front Evol Neurosci},
      school = {Department of Neuroscience, Georgetown University Washington, DC, USA.},
      year = {2011},
      volume = {2},
      pages = {111},
      url = {http://dx.doi.org/10.3389/fnevo.2010.00111},
      doi = {http://doi.org/10.3389/fnevo.2010.00111}
    }
    
    Vicini, S. The FGIN period: electrophysiological studies. 2011 Pharmacol Res
    Vol. 64(4), pp. 316-318School: Department of Physiology and Biophysics, Georgetown University Medical Center, room 225 3900 Reservoir Rd, N.W., Washington DC 20057, United States. svicin01@georgetown.edu 
    DOI URL 
    Abstract: This historical review of the electrophysiology laboratory complemented
    the activity of the various research teams at the Fidia Georgetown
    Institute for the Neurosciences and it was the fulfillment of Dr.
    Erminio Costa's dream to be able to study the inhibitory and excitatory
    synapse in the central nervous system. These studies were facilitated
    by the development of the patch clamp technique that allows the functional
    testing of several of the biochemical and pharmacological hypotheses.
    The studies described here were the results of the hard work of all
    the collaborators involved in the projects that will never forget
    the passionate and stimulating discussion with Dr Costa during and
    after the development of these projects.
    BibTeX:
    @article{Vicini2011,
      author = {Vicini, Stefano},
      title = {The FGIN period: electrophysiological studies.},
      journal = {Pharmacol Res},
      school = {Department of Physiology and Biophysics, Georgetown University Medical Center, room 225 3900 Reservoir Rd, N.W., Washington DC 20057, United States. svicin01@georgetown.edu},
      year = {2011},
      volume = {64},
      number = {4},
      pages = {316--318},
      url = {http://dx.doi.org/10.1016/j.phrs.2011.05.020},
      doi = {http://doi.org/10.1016/j.phrs.2011.05.020}
    }
    
    West, E.A., Forcelli, P.A., Murnen, A., Gale, K. & Malkova, L. A visual, position-independent instrumental reinforcer devaluation task for rats. 2011 J Neurosci Methods
    Vol. 194(2), pp. 297-304School: Interdisciplinary Program in Neuroscience, Georgetown University, 3970 Reservoir Rd NW, Washington, DC 20007, United States. eaw35@georgetown.edu 
    DOI URL 
    Abstract: Flexible goal-directed behavior has been studied across species using
    reinforcer devaluation tasks, in which subjects form associations
    between specific stimuli (cues) and specific reinforcer(s). The reinforcer
    is subsequently devalued by selective satiation or taste aversion.
    Following devaluation, subjects adjust their responding to the cues
    reflecting the new value of the reinforcer. Tasks currently used
    in rats differ in several ways from tasks used in monkeys and this
    may explain contrasting results between the two species. To address
    one of the differences, we developed a rat task independent of spatial
    cues. It employs two visual cues presented simultaneously, changing
    left and right positions pseudorandomly. Each cue predicts one of
    two food reinforcers. Rats were trained to lever press in response
    to the two visual cues. Subsequently, they were satiated on one of
    the foods followed by an extinction test where in each trial they
    could choose to respond to one of the two cues, one predicting the
    devalued reinforcer and the other the non-devalued. This procedure
    was repeated later with the alternative food devalued. The rats adjusted
    their responding by choosing the cue predicting the devalued food
    significantly less (p<0.05) than the alternative cue. These results
    show that rats can discriminate two visual stimuli presented simultaneously,
    devalue two different foods by selective satiation, and transfer
    the new value to the visual cues. Discrimination of the visual cues
    is not aided by spatial cues, thereby eliminating a major difference
    between the instrumental tasks used in rats and the task used in
    monkeys.
    BibTeX:
    @article{West2011,
      author = {Elizabeth A West and Patrick A Forcelli and Alice Murnen and Karen Gale and Ludise Malkova},
      title = {A visual, position-independent instrumental reinforcer devaluation task for rats.},
      journal = {J Neurosci Methods},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University, 3970 Reservoir Rd NW, Washington, DC 20007, United States. eaw35@georgetown.edu},
      year = {2011},
      volume = {194},
      number = {2},
      pages = {297--304},
      url = {http://dx.doi.org/10.1016/j.jneumeth.2010.11.004},
      doi = {http://doi.org/10.1016/j.jneumeth.2010.11.004}
    }
    
    Wu, J., Leung, P.Y., Sharp, A., Lee, H.J. & Wrathall, J.R. Increased expression of the close homolog of the adhesion molecule L1 in different cell types over time after rat spinal cord contusion. 2011 J Neurosci Res
    Vol. 89(5), pp. 628-638School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. jwu@anes.umm.edu 
    DOI URL 
    Abstract: The close homolog of the adhesion molecule L1 (CHL1) is important
    during CNS development, but a study with CHL1 knockout mice showed
    greater functional recovery after spinal cord injury (SCI) in its
    absence. We investigated CHL1 expression from 1 to 28 days after
    clinically relevant contusive SCI in Sprague-Dawley rats. Western
    blot analysis showed that CHL1 expression was significantly up-regulated
    at day 1 and further increased over 4 weeks after SCI. Immunohistochemistry
    of tissue sections showed that CHL1 in the intact spinal cord was
    expressed at low levels. By 1 day and through 4 weeks after SCI,
    CHL1 became highly expressed in NG2(+) cells. Hypertrophic GFAP(+)
    astrocytes also expressed CHL1 by 1 week after injury. The increase
    in CHL1 protein paralleled that of NG2 in the first week and GFAP
    between 1 and 4 weeks after injury. At 4 weeks, NG2(+) /CHL1(+) cells
    and GFAP(+) /CHL1(+) astrocytes were concentrated at the boundary
    between residual spinal cord tissue and the central lesion. NF200(+)
    spinal cord axons approached but did not penetrate this boundary.
    In contrast, CHL1(+) cells in the central lesion at 1 week and later
    colabeled with p75 and NG2 and were chronically associated with many
    NF200(+) axons, presumably axons that had sprouted in association
    with CHL1(+) Schwann cells infiltrating the cord after contusion.
    Thus, our study demonstrates up-regulation of CHL1 in multiple cell
    types and locations in a rat model of contusion injury and suggests
    that this molecule may be involved both in inhibition of axonal regeneration
    and in recovery processes after SCI.
    BibTeX:
    @article{Wu2011,
      author = {Junfang Wu and Philberta Y Leung and April Sharp and Hyun Joon Lee and Jean R Wrathall},
      title = {Increased expression of the close homolog of the adhesion molecule L1 in different cell types over time after rat spinal cord contusion.},
      journal = {J Neurosci Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. jwu@anes.umm.edu},
      year = {2011},
      volume = {89},
      number = {5},
      pages = {628--638},
      url = {http://dx.doi.org/10.1002/jnr.22598},
      doi = {http://doi.org/10.1002/jnr.22598}
    }
    
    Avdoshina, V., Biggio, F., Palchik, G., Campbell, L.A. & Mocchetti, I. Morphine induces the release of CCL5 from astrocytes: potential neuroprotective mechanism against the HIV protein gp120. 2010 Glia
    Vol. 58(13), pp. 1630-1639School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: A number of human immunodeficiency virus type-1 (HIV) positive subjects
    are also opiate abusers. These individuals are at high risk to develop
    neurological complications. However, little is still known about
    the molecular mechanism(s) linking opiates and HIV neurotoxicity.
    To learn more, we exposed rat neuronal/glial cultures prepared from
    different brain areas to opiate agonists and HIV envelope glycoproteins
    gp120IIIB or BaL. These strains bind to CXCR4 and CCR5 chemokine
    receptors, respectively, and promote neuronal death. Morphine did
    not synergize the toxic effect of gp120IIIB but inhibited the cytotoxic
    property of gp120BaL. This effect was blocked by naloxone and reproduced
    by the mu opioid receptor agonist DAMGO. To examine the potential
    mechanism(s) of neuroprotection, we determined the effect of morphine
    on the release of chemokines CCL5 and CXCL12 in neurons, astrocytes,
    and microglia cultures. CCL5 has been shown to prevent gp120BaL neurotoxicity
    while CXCL12 decreases neuronal survival. Morphine elicited a time-dependent
    release of CCL5 but failed to affect the release of CXCL12. This
    effect was observed only in primary cultures of astrocytes. To examine
    the role of endogenous CCL5 in the neuroprotective activity of morphine,
    mixed cerebellar neurons/glial cells were immunoneutralized against
    CCL5 prior to morphine and gp120 treatment. In these cells the neuroprotective
    effect of opiate agonists was blocked. Our data suggest that morphine
    may exhibit a neuroprotective activity against M-tropic gp120 through
    the release of CCL5 from astrocytes.
    BibTeX:
    @article{Avdoshina2010,
      author = {Valeriya Avdoshina and Francesca Biggio and Guillermo Palchik and Lee A Campbell and Italo Mocchetti},
      title = {Morphine induces the release of CCL5 from astrocytes: potential neuroprotective mechanism against the HIV protein gp120.},
      journal = {Glia},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2010},
      volume = {58},
      number = {13},
      pages = {1630--1639},
      url = {http://dx.doi.org/10.1002/glia.21035},
      doi = {http://doi.org/10.1002/glia.21035}
    }
    
    Bachis, A., Cruz, M.I. & Mocchetti, I. M-tropic HIV envelope protein gp120 exhibits a different neuropathological profile than T-tropic gp120 in rat striatum. 2010 Eur J Neurosci
    Vol. 32(4), pp. 570-578School: Department of Neuroscience, Georgetown University Medical Center, New Research Building, 3970 Reservoir Rd, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Most early human immunodeficiency virus type 1 (HIV-1) strains are
    macrophage (M)-tropic HIV variants and use the chemokine receptor
    CCR5 for infection. Neuronal loss and dementia are less severe among
    individuals infected with M-tropic strains. However, after several
    years, the T-cell (T)-tropic HIV strain, which uses the CXCR4 variant,
    can emerge in conjunction with brain abnormalities, suggesting strain-specific
    differences in neuropathogenicity. The molecular and cellular mechanisms
    of such diversity remain under investigation. We have previously
    demonstrated that HIV envelope protein gp120IIIB, which binds to
    CXCR4, causes neuronal apoptosis in rodents. Thus, we have used a
    similar experimental model to examine the neurotoxic effects of M-tropic
    gp120BaL. gp120BaL was microinjected in the rat striatum and neuronal
    apoptosis was examined in the striatum, as well as in anatomically
    connected areas, such as the somatosensory cortex and the substantia
    nigra. gp120BaL promoted neuronal apoptosis and tissue loss that
    were confined to the striatum. Apoptosis was associated with microglial
    activation and increased levels of interleukin-1beta. Intriguingly,
    gp120BaL increased brain-derived neurotrophic factor in the striatum.
    Overall, our data show that gp120BaL demonstrates a different neuropathological
    profile than gp120IIIB. A better understanding of the pathogenic
    mechanisms mediating HIV neurotoxicity is vital for developing effective
    neuroprotective therapies against AIDS-associated dementia complex.
    BibTeX:
    @article{Bachis2010,
      author = {Alessia Bachis and Maria I Cruz and Italo Mocchetti},
      title = {M-tropic HIV envelope protein gp120 exhibits a different neuropathological profile than T-tropic gp120 in rat striatum.},
      journal = {Eur J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, New Research Building, 3970 Reservoir Rd, Washington, DC 20057, USA.},
      year = {2010},
      volume = {32},
      number = {4},
      pages = {570--578},
      url = {http://dx.doi.org/10.1111/j.1460-9568.2010.07325.x},
      doi = {http://doi.org/10.1111/j.1460-9568.2010.07325.x}
    }
    
    Burns, M.P. & Rebeck, G.W. Intracellular cholesterol homeostasis and amyloid precursor protein processing. 2010 Biochim Biophys Acta
    Vol. 1801(8), pp. 853-859School: Georgetown University Medical Center, Department of Neuroscience, Washington, DC 20057, USA. mpb37@georgetown.edu 
    DOI URL 
    Abstract: Many preclinical and clinical studies have implied a role for cholesterol
    in the pathogenesis of Alzheimer's disease (AD). In this review we
    will discuss the movement of intracellular cholesterol and how normal
    distribution, transport, and export of cholesterol are vital for
    regulation of the AD related protein, Abeta. We focus on cholesterol
    distribution in the plasma membrane, transport through the endosomal/lysosomal
    system, control of cholesterol intracellular signaling at the endoplasmic
    reticulum and Golgi, the HMG-CoA reductase pathway and finally export
    of cholesterol from the cell.
    BibTeX:
    @article{Burns2010,
      author = {Mark P Burns and G. William Rebeck},
      title = {Intracellular cholesterol homeostasis and amyloid precursor protein processing.},
      journal = {Biochim Biophys Acta},
      school = {Georgetown University Medical Center, Department of Neuroscience, Washington, DC 20057, USA. mpb37@georgetown.edu},
      year = {2010},
      volume = {1801},
      number = {8},
      pages = {853--859},
      url = {http://dx.doi.org/10.1016/j.bbalip.2010.03.004},
      doi = {http://doi.org/10.1016/j.bbalip.2010.03.004}
    }
    
    Byrnes, K.R., Fricke, S.T. & Faden, A.I. Neuropathological differences between rats and mice after spinal cord injury. 2010 J Magn Reson Imaging
    Vol. 32(4), pp. 836-846School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: To investigate the utility of noninvasive magnetic resonance imaging
    (MRI) protocols to demonstrate pathological differences between rats
    and mice after spinal cord injury (SCI). Rats and mice are commonly
    used to model SCI; however, histology and immunohistochemistry have
    shown differences in neuropathology between the two species, including
    cavity formation and scar/inflammatory responses.Moderate contusion
    SCI was performed on adult male rats and mice. At 28 days postinjury,
    animals underwent T1-weighted (T1W), with or without gadolinium contrast,
    or T2-weighted (T2W) magnetic resonance imaging (MRI), to be compared
    with histology at the same timepoint.In both species, all MRI methods
    demonstrated changes in spinal cord anatomy. Immunohistochemistry
    indicated that T2W accurately reflected areas of inflammation and
    glial scar formation in rats and mice. Quantitation of lesion volume
    by histology and functional performance correlated best with T2W
    measurements in both species. Gadolinium contrast accurately reflected
    the blood-spinal cord-barrier permeability in both species, which
    appeared greater in rats than in mice.These data demonstrate that
    MRI, with either a T1W or T2W protocol, can effectively distinguish
    pathological differences between rats and mice.
    BibTeX:
    @article{Byrnes2010,
      author = {Kimberly R Byrnes and Stanley T Fricke and Alan I Faden},
      title = {Neuropathological differences between rats and mice after spinal cord injury.},
      journal = {J Magn Reson Imaging},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2010},
      volume = {32},
      number = {4},
      pages = {836--846},
      url = {http://dx.doi.org/10.1002/jmri.22323},
      doi = {http://doi.org/10.1002/jmri.22323}
    }
    
    Cartagena, C.M., Burns, M.P. & Rebeck, G.W. 24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury. 2010 Brain Res
    Vol. 1319, pp. 1-12School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Membrane damage during traumatic brain injury (TBI) alters the brain
    homeostasis of cholesterol and other lipids. Cholesterol 24S-hydroxylase
    (Cyp46) is a cholesterol metabolic enzyme that is increased after
    TBI. Here, we systematically examined the effects of the enzymatic
    product of Cyp46, 24S-hydroxycholesterol, on the cholesterol regulatory
    genes, SREBP-1 and 2, their posttranslational regulation, and their
    effects on gene transcription. 24S-hydroxycholesterol increased levels
    of SREBP-1 mRNA and full-length protein but did not change levels
    of cleaved SREBP-1, consistent with the role of 24-hydroxycholesterol
    as an LXR agonist. In contrast, 24S-hydroxycholesterol decreased
    levels of LXR-independent SREBP-2 mRNA, full-length protein, and
    SREBP-2 active cleavage product. We examined the downstream effects
    of changes to these lipid regulatory factors by studying cholesterol
    and fatty acid synthesis genes. In neuroblastoma cells, 24S-hydroxycholesterol
    decreased mRNA levels of the cholesterol synthesis genes HMG CoA
    reductase, squalene synthase, and FPP synthase but did not alter
    levels of the mRNA of fatty acid synthesis genes acetyl CoA carboxylase
    or fatty acid synthase. After TBI, as after 24S-hydroxycholesterol
    treatment in vitro, SREBP-1 mRNA levels were increased while SREBP-2
    mRNA levels were decreased. Also similar to the in vitro results
    with 24S-hydroxycholesterol, HMG CoA reductase and squalene synthase
    mRNA levels were significantly decreased. Fatty acid synthase mRNA
    levels were not altered but acetyl CoA carboxylase mRNA levels were
    significantly decreased. Thus, changes to transcription of cholesterol
    synthesis genes after TBI were consistent with increases in Cyp46
    activity, but changes to fatty acid synthesis genes must be regulated
    by other mechanisms.
    BibTeX:
    @article{Cartagena2010,
      author = {Casandra M Cartagena and Mark P Burns and G. William Rebeck},
      title = {24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic brain injury.},
      journal = {Brain Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057, USA.},
      year = {2010},
      volume = {1319},
      pages = {1--12},
      url = {http://dx.doi.org/10.1016/j.brainres.2009.12.080},
      doi = {http://doi.org/10.1016/j.brainres.2009.12.080}
    }
    
    Cernak, I., Chang, T., Ahmed, F.A., Cruz, M.I., Vink, R., Stoica, B. & Faden, A.I. Pathophysiological response to experimental diffuse brain trauma differs as a function of developmental age. 2010 Dev Neurosci
    Vol. 32(5-6), pp. 442-453School: Department of Neuroscience, Georgetown University Medical Center, Washington, D.C., USA. 
    DOI URL 
    Abstract: The purpose of experimental models of traumatic brain injury (TBI)
    is to reproduce selected aspects of human head injury such as brain
    edema, contusion or concussion, and functional deficits, among others.
    As the immature brain may be particularly vulnerable to injury during
    critical periods of development, and pediatric TBI may cause neurobehavioral
    deficits, our aim was to develop and characterize as a function of
    developmental age a model of diffuse TBI (DTBI) with quantifiable
    functional deficits. We modified a DTBI rat model initially developed
    by us in adult animals to study the graded response to injury as
    a function of developmental age - 7-, 14- and 21-day-old rats compared
    to young adult (3-month-old) animals. Our model caused motor deficits
    that persisted even after the pups reached adulthood, as well as
    reduced cognitive performance 2 weeks after injury. Moreover, our
    model induced prominent edema often seen in pediatric TBI, particularly
    evident in 7- and 14-day-old animals, as measured by both the wet
    weight/dry weight method and diffusion-weighted MRI. Blood-brain
    barrier permeability, as measured by the Evans blue dye technique,
    peaked at 20 min after trauma in all age groups, with a second peak
    found only in adult animals at 24 h after injury. Phosphorus MR spectroscopy
    showed no significant changes in the brain energy metabolism of immature
    rats with moderate DTBI, in contrast to significant decreases previously
    identified in adult animals.
    BibTeX:
    @article{Cernak2010,
      author = {Ibolja Cernak and Taeun Chang and Farid A Ahmed and Maria I Cruz and Robert Vink and Bogdan Stoica and Alan I Faden},
      title = {Pathophysiological response to experimental diffuse brain trauma differs as a function of developmental age.},
      journal = {Dev Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, D.C., USA.},
      year = {2010},
      volume = {32},
      number = {5-6},
      pages = {442--453},
      url = {http://dx.doi.org/10.1159/000320085},
      doi = {http://doi.org/10.1159/000320085}
    }
    
    Conant, K., Lonskaya, I., Szklarczyk, A., Krall, C., Steiner, J., Maguire-Zeiss, K. & Lim, S.T. Methamphetamine-associated cleavage of the synaptic adhesion molecule intercellular adhesion molecule-5. 2010 J NeurochemSchool: The Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA The Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.  DOI URL 
    Abstract: J. Neurochem. (2011) 10.1111/j.1471-4159.2010.07153.x ABSTRACT: Methamphetamine
    (MA) is a highly addictive psychostimulant that, used in excess,
    may be neurotoxic. Although the mechanisms that underlie its addictive
    potential are not completely understood, in animal models matrix
    metalloproteinase (MMP) inhibitors can reduce behavioral correlates
    of addiction. In addition, evidence from genome-wide association
    studies suggests that polymorphisms in synaptic cell-adhesion molecules
    (CAMs), known MMP substrates, are linked to addictive potential in
    humans. In the present study, we examined the ability of MA to stimulate
    cleavage of intercellular adhesion molecule-5 (ICAM-5), a synaptic
    CAM expressed on dendritic spines in the telencephalon. Previous
    studies have shown that shedding of ICAM-5 is associated with maturation
    of dendritic spines, and that MMP-dependent shedding occurs with
    long term potentiation. Herein, we show that MA stimulates ectodomain
    cleavage of ICAM-5 in vitro, and that this is abrogated by a broad
    spectrum MMP inhibitor. We also show that an acute dose of MA, administered
    in vivo, is associated with cleavage of ICAM-5 in murine hippocampus
    and striatum. This occurs within 6 h and is accompanied by an increase
    in MMP-9 protein. In related experiments, we examined the potential
    consequences of ICAM-5 shedding. We demonstrate that the ICAM-5 ectodomain
    can interact with ?(1) integrins, and that it can stimulate ?(1)
    integrin-dependent phosphorylation of cofilin, an event that has
    previously been linked to MMP-dependent spine maturation. Together
    these data support an emerging appreciation of MMPs as effectors
    of synaptic plasticity and suggest a mechanism by which MA may influence
    the same.
    BibTeX:
    @article{Conant2010,
      author = {Katherine Conant and Irina Lonskaya and Arek Szklarczyk and Caroline Krall and Joseph Steiner and Kathleen Maguire-Zeiss and Seung T Lim},
      title = {Methamphetamine-associated cleavage of the synaptic adhesion molecule intercellular adhesion molecule-5.},
      journal = {J Neurochem},
      school = {The Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA The Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.},
      year = {2010},
      url = {http://dx.doi.org/10.1111/j.1471-4159.2010.07153.x},
      doi = {http://doi.org/10.1111/j.1471-4159.2010.07153.x}
    }
    
    Conant, K., Wang, Y., Szklarczyk, A., Dudak, A., Mattson, M.P. & Lim, S.T. Matrix metalloproteinase-dependent shedding of intercellular adhesion molecule-5 occurs with long-term potentiation. 2010 Neuroscience
    Vol. 166(2), pp. 508-521School: Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. kec84@georgetown.edu 
    DOI URL 
    Abstract: Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases
    that can be released or activated in a neuronal activity dependent
    manner. Although pathologically elevated levels of MMPs may be synaptotoxic,
    physiologically appropriate levels of MMPs may instead enhance synaptic
    transmission. MMP inhibitors can block long term potentiation (LTP),
    and at least one family member can affect an increase in the volume
    of dendritic spines. While the mechanism by which MMPs affect these
    changes is not completely understood, one possibility is that the
    cleavage of specific synaptic cell adhesion molecules plays a role.
    In the present study, we have examined the ability of neuronal activity
    to stimulate rapid MMP dependent shedding of the intercellular adhesion
    molecule-5 (ICAM-5), a synaptic adhesion molecule that is thought
    to inhibit the maturation and enlargement of dendritic spines. Since
    such cleavage would likely occur within minutes if it were relevant
    to a process such as LTP, we focused on post stimulus time points
    of 30 min or less. We show that NMDA can stimulate rapid shedding
    of ICAM-5 from cortical neurons in dissociated cell cultures and
    that such shedding is diminished by pretreatment of cultures with
    inhibitors that target MMP-3 and -9, proteases thought to influence
    synaptic plasticity. Additional studies suggest that MMP mediated
    cleavage of ICAM-5 occurs at amino acid 780, so that the major portion
    of the ectodomain is released. Since reductions in ICAM-5 have been
    linked to changes in dendritic spine morphology that are associated
    with LTP, we also examined the possibility that MMP dependent ICAM-5
    shedding occurs following high frequency tetanic stimulation of murine
    hippocampal slices. Results show that the shedding of ICAM-5 occurs
    in association with LTP, and that both LTP and the associated ICAM-5
    shedding are reduced when slices are pretreated with an MMP inhibitor.
    Together, these findings suggest that neuronal activity is linked
    to the shedding of a molecule that may inhibit dendritic spine enlargement
    and that MMPs can affect this change. While further studies will
    be necessary to determine the extent to which cleavage of ICAM-5
    in particular contributes to MMP dependent LTP, our data support
    an emerging body of literature suggesting that MMPs are critical
    mediators of synaptic plasticity.
    BibTeX:
    @article{Conant2010a,
      author = {Conant, K. and Wang, Y. and Szklarczyk, A. and Dudak, A. and Mattson, M. P. and Lim, S. T.},
      title = {Matrix metalloproteinase-dependent shedding of intercellular adhesion molecule-5 occurs with long-term potentiation.},
      journal = {Neuroscience},
      school = {Department of Neurology, Johns Hopkins University, Baltimore, MD, USA. kec84@georgetown.edu},
      year = {2010},
      volume = {166},
      number = {2},
      pages = {508--521},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2009.12.061},
      doi = {http://doi.org/10.1016/j.neuroscience.2009.12.061}
    }
    
    Feng, L.R., Federoff, H.J., Vicini, S. & Maguire-Zeiss, K.A. Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability. 2010 Eur J Neurosci
    Vol. 32(1), pp. 10-17School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: alpha-Synuclein has been linked to the pathogenesis of Parkinson's
    disease and other synucleinopathies through its propensity to form
    toxic oligomers. The exact mechanism for oligomeric synuclein-directed
    cell vulnerability has not been fully elucidated, but one hypothesis
    portends the formation of synuclein-containing pores within cell
    membranes leading to leak channel-mediated calcium influx and subsequent
    cell death. Here we demonstrate synuclein-induced formation of sodium
    dodecyl sulfate-stable oligomers, intracellular synuclein-positive
    aggregates, alterations in membrane conductance reminiscent of leak
    channels and subsequent cytotoxicity in a dopaminergic-like cell
    line. Furthermore we demonstrate that the synuclein-induced membrane
    conductance changes are blocked by direct extracellular application
    of an anti-synuclein antibody. The work presented here confirms that
    synuclein overexpression leads to membrane conductance changes and
    demonstrates for the first time through antibody-blocking studies
    that synuclein plays a direct role in the formation of leak channels.
    BibTeX:
    @article{Feng2010,
      author = {Li Rebekah Feng and Howard J Federoff and Stefano Vicini and Kathleen A Maguire-Zeiss},
      title = {Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability.},
      journal = {Eur J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2010},
      volume = {32},
      number = {1},
      pages = {10--17},
      url = {http://dx.doi.org/10.1111/j.1460-9568.2010.07266.x},
      doi = {http://doi.org/10.1111/j.1460-9568.2010.07266.x}
    }
    
    Feng, L.R. & Maguire-Zeiss, K.A. Gene therapy in Parkinson's disease: rationale and current status. 2010 CNS Drugs
    Vol. 24(3), pp. 177-192School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Parkinson's disease is the second most common age-related neurodegenerative
    disorder, typified by the progressive loss of substantia nigra pars
    compacta dopamine neurons and the consequent decrease in the neurotransmitter
    dopamine. Patients exhibit a range of clinical symptoms, with the
    most common affecting motor function and including resting tremor,
    rigidity, akinesia, bradykinesia and postural instability. Current
    pharmacological interventions are palliative and largely aimed at
    increasing dopamine levels through increased production and/or inhibition
    of metabolism of this key neurotransmitter. The gold standard for
    treatment of both familial and sporadic Parkinson's disease is the
    peripheral administration of the dopamine precursor, levodopa. However,
    many patients gradually develop levodopa-induced dyskinesias and
    motor fluctuations. In addition, dopamine enhancement therapies are
    most useful when a portion of the nigrostriatal pathway is intact.
    Consequently, as the number of substantia nigra dopamine neurons
    and striatal projections decrease, these treatments become less efficacious.
    Current translational research is focused on the development of novel
    disease-modifying therapies, including those utilizing gene therapeutic
    approaches. Herein we present an overview of current gene therapy
    clinical trials for Parkinson's disease. Employing either recombinant
    adeno-associated virus type 2 (rAAV2) or lentivirus vectors, these
    clinical trials are focused on three overarching approaches: augmentation
    of dopamine levels via increased neurotransmitter production; modulation
    of the neuronal phenotype; and neuroprotection. The first two therapies
    discussed in this article focus on increasing dopamine production
    via direct delivery of genes involved in neurotransmitter synthesis
    (amino acid decarboxylase, tyrosine hydroxylase and GTP [guanosine
    triphosphate] cyclohydrolase 1). In an attempt to bypass the degenerating
    nigrostriatal pathway, a third clinical trial utilizes rAAV2 to deliver
    glutamic acid decarboxylase to the subthalamic nucleus, converting
    a subset of excitatory neurons to GABA-producing cells. In contrast,
    the final clinical trial is aimed at protecting the degenerating
    nigrostriatum by striatal delivery of rAAV2 harbouring the neuroprotective
    gene, neurturin. Based on preclinical studies, this gene therapeutic
    approach is posited to slow disease progression by enhancing neuronal
    survival. In addition, we discuss the outcome of each clinical trial
    and discuss the potential rationale for the marginal yet incremental
    clinical advancements that have thus far been realized for Parkinson's
    disease gene therapy.
    BibTeX:
    @article{Feng2010a,
      author = {Li Rebekah Feng and Kathleen A Maguire-Zeiss},
      title = {Gene therapy in Parkinson's disease: rationale and current status.},
      journal = {CNS Drugs},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2010},
      volume = {24},
      number = {3},
      pages = {177--192},
      url = {http://dx.doi.org/10.2165/11533740-000000000-00000},
      doi = {http://doi.org/10.2165/11533740-000000000-00000}
    }
    
    Forcelli, P.A., Janssen, M.J., Stamps, L.A., Sweeney, C., Vicini, S. & Gale, K. Therapeutic strategies to avoid long-term adverse outcomes of neonatal antiepileptic drug exposure. 2010 Epilepsia
    Vol. 51 Suppl 3, pp. 18-23School: Department of Pharmacology, Georgetown University, Washington, District of Columbia 20057, USA. 
    DOI URL 
    Abstract: Antiepileptic drugs (AEDs) such as phenobarbital, phenytoin, and valproic
    acid, when given in therapeutic doses to neonatal rats, cause pronounced
    neuronal apoptotic cell death. This effect is especially pronounced
    in the striatum and cortex during the second postnatal week, a period
    corresponding to the "brain growth spurt" (third trimester of gestation
    and early infancy) in humans. Of particular concern is the fact that
    phenobarbital is the most frequently used therapy for neonatal epilepsy.
    If AED-induced neuronal cell death leads to long-term functional
    impairment, then it becomes crucial to find therapies that avoid
    this neurotoxicity in the sensitive period. Herein we examine short-
    and long-term functional effects following exposure of neonatal rat
    pups to phenobarbital; the functions tested include striatal gamma-aminobutyric
    acid (GABA)ergic synaptic responses and reflex development in pups,
    and fear conditioning, emotionality, and sensory-motor gating in
    adults. In all cases, phenobarbital exposure during the second postnatal
    week was sufficient to cause significant impairment. In contrast,
    adult animals exposed as pups to lamotrigine (given in a dose that
    does not cause apoptotic neuronal death) were not impaired on the
    tasks we examined. Our data suggest that treatments devoid of proapoptotic
    actions may be promising therapies for avoiding adverse outcomes
    after neonatal exposure. In addition, our findings identify early
    exposure to certain AEDs as an important potential risk factor contributing
    to psychiatric and neurologic abnormalities later in life.
    BibTeX:
    @article{Forcelli2010,
      author = {Patrick A Forcelli and Megan J Janssen and Lauren A Stamps and Cameron Sweeney and Stefano Vicini and Karen Gale},
      title = {Therapeutic strategies to avoid long-term adverse outcomes of neonatal antiepileptic drug exposure.},
      journal = {Epilepsia},
      school = {Department of Pharmacology, Georgetown University, Washington, District of Columbia 20057, USA.},
      year = {2010},
      volume = {51 Suppl 3},
      pages = {18--23},
      url = {http://dx.doi.org/10.1111/j.1528-1167.2010.02603.x},
      doi = {http://doi.org/10.1111/j.1528-1167.2010.02603.x}
    }
    
    Hoe, H.-S., Lee, H.-K. & Pak, D.T.S. The Upside of APP at Synapses. 2010 CNS Neurosci TherSchool: ?Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA Department of Neurology, Georgetown University Medical Center, Washington, DC, USA Department of Biology, College of Chemical and Life Sciences, University of Maryland, College Park, MD, USA Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.  DOI URL 
    Abstract: The memory dysfunctions that characterize Alzheimer's disease (AD)
    are strongly correlated with synapse loss. The amyloid precursor
    protein (APP) and its cleavage product AΒ play central roles in synapse
    and memory loss, and thus are strongly implicated in the pathogenesis
    of AD. Numerous in vitro and transgenic AD mouse model studies have
    shown that overexpression of APP leads to AΒ accumulation, which
    causes decreased synaptic activity and dendritic spine density. However,
    the normal synaptic function of APP itself is not fully understood.
    Several recent studies have found that full-length APP promotes synaptic
    activity, synapse formation, and dendritic spine formation. These
    findings cast APP as a potential key player in learning and memory.
    It is of interest that the synaptic functions of full-length APP
    are opposite to the effects associated with pathological AΒ accumulation.
    In this review, we will summarize the normal functions of APP at
    synapses and spines along with other known functions of APP, including
    its role in cell motility, neuronal migration, and neurite outgrowth.
    These studies shed light on the physiological actions of APP, independent
    of AΒ effects, and thus lead to a better understanding of the synaptic
    dysfunctions associated with AD.
    BibTeX:
    @article{Hoe2010,
      author = {Hyang-Sook Hoe and Hey-Kyoung Lee and Daniel T S Pak},
      title = {The Upside of APP at Synapses.},
      journal = {CNS Neurosci Ther},
      school = {?Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA Department of Neurology, Georgetown University Medical Center, Washington, DC, USA Department of Biology, College of Chemical and Life Sciences, University of Maryland, College Park, MD, USA Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2010},
      url = {http://dx.doi.org/10.1111/j.1755-5949.2010.00221.x},
      doi = {http://doi.org/10.1111/j.1755-5949.2010.00221.x}
    }
    
    Khandelwal, P.J., Dumanis, S.B., Feng, L.R., Maguire-Zeiss, K., Rebeck, G., Lashuel, H.A. & Moussa, C.E. Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model. 2010 Mol Neurodegener
    Vol. 5, pp. 47School: Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu. 
    DOI URL 
    Abstract: ABSTRACT:α-synuclein aggregates in Lewy bodies and plays a central
    role in the pathogenesis of a group of neurodegenerative disorders,
    known as "Synucleinopathies", including Parkinson's disease. Parkin
    mutations result in loss of parkin E3-ubiquitin ligase activity and
    cause autosomal recessive early onset parkinsonism.We tested how
    these two genes interact by examining the effects of parkin on post-translational
    modification of α-synuclein in gene transfer animal models, using
    a lentiviral gene delivery system into the striatum of 2-month old
    male Sprague Dawley rats.Viral expression of wild type α-synuclein
    caused accumulation of α-synuclein and was associated with increased
    cell death and inflammation. α-synuclein increased PLK2 levels and
    GSK-3? activity and increased the levels of phosphorylated α-synuclein
    and Tau. Parkin co-expression reduced the levels of phosphorylated
    α-synuclein and attenuated cell death and inflammation. Parkin reduced
    PLK2 levels and increased PP2A activation.These data suggest that
    parkin reduces α-synuclein levels and alters the balance between
    phosphatase and kinase activities that affect the levels of phosphorylated
    α-synuclein. These results indicate novel mechanisms for parkin protection
    against α-synuclein-induced toxicity in PD.
    BibTeX:
    @article{Khandelwal2010,
      author = {Preeti J Khandelwal and Sonya B Dumanis and Li Rebekah Feng and Kathleen Maguire-Zeiss and Gw Rebeck and Hilal A Lashuel and Charbel Eh Moussa},
      title = {Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu.},
      year = {2010},
      volume = {5},
      pages = {47},
      url = {http://dx.doi.org/10.1186/1750-1326-5-47},
      doi = {http://doi.org/10.1186/1750-1326-5-47}
    }
    
    Khandelwal, P.J., Dumanis, S.B., Feng, L.R., Maguire-Zeiss, K., Rebeck, G., Lashuel, H.A. & Moussa, C.E. Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model. 2010 Mol Neurodegener
    Vol. 5, pp. 47School: Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu. 
    DOI URL 
    Abstract: α-synuclein aggregates in Lewy bodies and plays a central role in
    the pathogenesis of a group of neurodegenerative disorders, known
    as "Synucleinopathies", including Parkinson's disease. Parkin mutations
    result in loss of parkin E3-ubiquitin ligase activity and cause autosomal
    recessive early onset parkinsonism.We tested how these two genes
    interact by examining the effects of parkin on post-translational
    modification of α-synuclein in gene transfer animal models, using
    a lentiviral gene delivery system into the striatum of 2-month old
    male Sprague Dawley rats.Viral expression of wild type α-synuclein
    caused accumulation of α-synuclein and was associated with increased
    cell death and inflammation. α-synuclein increased PLK2 levels and
    GSK-3Beta activity and increased the levels of phosphorylated α-synuclein
    and Tau. Parkin co-expression reduced the levels of phosphorylated
    α-synuclein and attenuated cell death and inflammation. Parkin reduced
    PLK2 levels and increased PP2A activation.These data suggest that
    parkin reduces α-synuclein levels and alters the balance between
    phosphatase and kinase activities that affect the levels of phosphorylated
    α-synuclein. These results indicate novel mechanisms for parkin protection
    against α-synuclein-induced toxicity in PD.
    BibTeX:
    @article{Khandelwal2010b,
      author = {Khandelwal, Preeti J. and Dumanis, Sonya B. and Feng, Li Rebekah and Maguire-Zeiss, Kathleen and Rebeck, Gw and Lashuel, Hilal A. and Moussa, Charbel Eh},
      title = {Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu.},
      year = {2010},
      volume = {5},
      pages = {47},
      url = {http://dx.doi.org/10.1186/1750-1326-5-47},
      doi = {http://doi.org/10.1186/1750-1326-5-47}
    }
    
    Khandelwal, P.J., Dumanis, S.B., Feng, L.R., Maguire-Zeiss, K., Rebeck, G., Lashuel, H.A. & Moussa, C.E. Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model. 2010 Mol Neurodegener
    Vol. 5, pp. 47School: Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu. 
    DOI URL 
    Abstract: α-synuclein aggregates in Lewy bodies and plays a central role in
    the pathogenesis of a group of neurodegenerative disorders, known
    as "Synucleinopathies", including Parkinson's disease. Parkin mutations
    result in loss of parkin E3-ubiquitin ligase activity and cause autosomal
    recessive early onset parkinsonism.We tested how these two genes
    interact by examining the effects of parkin on post-translational
    modification of α-synuclein in gene transfer animal models, using
    a lentiviral gene delivery system into the striatum of 2-month old
    male Sprague Dawley rats.Viral expression of wild type α-synuclein
    caused accumulation of α-synuclein and was associated with increased
    cell death and inflammation. α-synuclein increased PLK2 levels and
    GSK-3Beta activity and increased the levels of phosphorylated α-synuclein
    and Tau. Parkin co-expression reduced the levels of phosphorylated
    α-synuclein and attenuated cell death and inflammation. Parkin reduced
    PLK2 levels and increased PP2A activation.These data suggest that
    parkin reduces α-synuclein levels and alters the balance between
    phosphatase and kinase activities that affect the levels of phosphorylated
    α-synuclein. These results indicate novel mechanisms for parkin protection
    against α-synuclein-induced toxicity in PD.
    BibTeX:
    @article{Khandelwal2010d,
      author = {Khandelwal, Preeti J. and Dumanis, Sonya B. and Feng, Li Rebekah and Maguire-Zeiss, Kathleen and Rebeck, Gw and Lashuel, Hilal A. and Moussa, Charbel Eh},
      title = {Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington D,C, U,S,A, 20007. cem46@georgetown.edu.},
      year = {2010},
      volume = {5},
      pages = {47},
      url = {http://dx.doi.org/10.1186/1750-1326-5-47},
      doi = {http://doi.org/10.1186/1750-1326-5-47}
    }
    
    Khandelwal, P.J., Dumanis, S.B., Feng, L.R., Maguire-Zeiss, K., Rebeck, G., Lashuel, H.A. & Moussa, C.E. Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model. 2010 Mol Neurodegener
    Vol. 5, pp. 47School: r, Washington D,C, U,S,A, 20007. cem46@georgetown.edu. 
    DOI URL 
    Abstract: α-synuclein aggregates in Lewy bodies and plays a central role in
    the pathogenesis of a group of neurodegenerative disorders, known
    as "Synucleinopathies", including Parkinson's disease. Parkin mutations
    result in loss of parkin E3-ubiquitin ligase activity and cause autosomal
    recessive early onset parkinsonism.We tested how these two genes
    interact by examining the effects of parkin on post-translational
    modification of α-synuclein in gene transfer animal models, using
    a lentiviral gene delivery system into the striatum of 2-month old
    male Sprague Dawley rats.Viral expression of wild type α-synuclein
    caused accumulation of α-synuclein and was associated with increased
    cell death and inflammation. α-synuclein increased PLK2 levels and
    GSK-3Beta activity and increased the levels of phosphorylated α-synuclein
    and Tau. Parkin co-expression reduced the levels of phosphorylated
    α-synuclein and attenuated cell death and inflammation. Parkin reduced
    PLK2 levels and increased PP2A activation.These data suggest that
    parkin reduces α-synuclein levels and alters the balance between
    phosphatase and kinase activities that affect the levels of phosphorylated
    α-synuclein. These results indicate novel mechanisms for parkin protection
    against α-synuclein-induced toxicity in PD.
    BibTeX:
    @article{Khandelwal2010e,
      author = {Khandelwal, Preeti J. and Dumanis, Sonya B. and Feng, Li Rebekah and Maguire-Zeiss, Kathleen and Rebeck, Gw and Lashuel, Hilal A. and Moussa, Charbel Eh},
      title = {Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model.},
      journal = {Mol Neurodegener},
      school = {r, Washington D,C, U,S,A, 20007. cem46@georgetown.edu.},
      year = {2010},
      volume = {5},
      pages = {47},
      url = {http://dx.doi.org/10.1186/1750-1326-5-47},
      doi = {http://doi.org/10.1186/1750-1326-5-47}
    }
    
    Khandelwal, P.J. & Moussa, C.E.-H. The Relationship between Parkin and Protein Aggregation in Neurodegenerative Diseases. 2010 Front Psychiatry
    Vol. 1, pp. 15School: Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: The most prominent changes in neurodegenerative diseases are protein
    accumulation and inclusion formation. Several neurodegenerative diseases,
    including Alzheimer's, the Synucleinopathies and Tauopathies share
    several overlapping clinical symptoms manifest in Parkinsonism, cognitive
    decline and dementia. As degeneration progresses in the disease process,
    clinical symptoms suggest convergent pathological pathways. Biochemically,
    protein cleavage, ubiquitination and phosphorylation seem to play
    fundamental roles in protein aggregation, inclusion formation and
    inflammatory responses. In the following we provide a synopsis of
    the current knowledge about protein accumulation and astrogliosis
    as a common denominator in neurodegenerative diseases, and we propose
    insights into protein degradation and anti-inflammation. We review
    the E3-ubiquitin ligase and other possible functions of parkin as
    a suppressant of inflammatory signs and a strategy to clear amyloid
    proteins in neurodegenerative diseases.
    BibTeX:
    @article{Khandelwal2010a,
      author = {Preeti J Khandelwal and Charbel E-H Moussa},
      title = {The Relationship between Parkin and Protein Aggregation in Neurodegenerative Diseases.},
      journal = {Front Psychiatry},
      school = {Department of Neuroscience, Georgetown University Medical Center Washington, DC, USA.},
      year = {2010},
      volume = {1},
      pages = {15},
      url = {http://dx.doi.org/10.3389/fpsyt.2010.00015},
      doi = {http://doi.org/10.3389/fpsyt.2010.00015}
    }
    
    Kim, J., Gale, K. & Kondratyev, A. Effects of repeated minimal electroshock seizures on NGF, BDNF and FGF-2 protein in the rat brain during postnatal development. 2010 Int J Dev Neurosci
    Vol. 28(3), pp. 227-232School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Repeated brief seizures, such as those induced by electroconvulsive
    therapy (ECT), markedly elevate neurotrophic factor levels in the
    adult rat brain, but it is not known whether a similar response to
    seizures occurs in immature animals. To address this question, we
    evoked brief seizures with electroconvulsive shock (ECS) in rat pups
    at different stages of postnatal development and examined basic fibroblast
    growth factor (FGF-2), nerve growth factor (NGF), and brain-derived
    neurotrophic factor (BDNF) proteins in selected brain regions in
    which these trophic factors are known to increase in the adult rat
    following ECS-induced seizures. ECS treatments were administered
    daily (3 episodes/day) over 7 days to rat pups of three different
    ages: postnatal day (P)1-7, P7-13, or P14-20. Protein levels were
    measured 6h after the last ECS using Western blotting for FGF-2 in
    rhinal cortex, ELISA for BDNF and NGF in hippocampus, and NGF in
    frontal cortex. 7 days of repeated ECS-induced seizures during P1-7
    did not alter protein levels for BDNF, FGF-2, or NGF. The repeated
    seizures during P7-13 affected only BDNF protein, causing a significant
    elevation of 40% in hippocampus over sham-treated controls. In P14-20
    pups, the repeated seizures resulted in a significant increase in
    BDNF in hippocampus (162% over controls) and FGF-2 in rhinal cortex
    (34% over controls), while NGF protein did not show a significant
    change in either hippocampus or frontal cortex. The results suggest
    that during the first postnatal week there is a resistance to seizure-induced
    increase in neurotrophic factors, but by the third postnatal week,
    both BDNF and FGF-2 are elevated substantially in response to repeated
    seizures. This time-dependent profile suggests that synthesis of
    these proteins is initially activity-independent, becoming subject
    to activity-dependent regulation by 3 weeks of age. This maturation
    of seizure-evoked changes in trophic factors may be important for
    understanding the impact of ECT and seizures in childhood.
    BibTeX:
    @article{Kim2010a,
      author = {Jinsook Kim and Karen Gale and Alexei Kondratyev},
      title = {Effects of repeated minimal electroshock seizures on NGF, BDNF and FGF-2 protein in the rat brain during postnatal development.},
      journal = {Int J Dev Neurosci},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2010},
      volume = {28},
      number = {3},
      pages = {227--232},
      url = {http://dx.doi.org/10.1016/j.ijdevneu.2010.02.003},
      doi = {http://doi.org/10.1016/j.ijdevneu.2010.02.003}
    }
    
    Kim, J., Lilliehook, C., Dudak, A., Prox, J., Saftig, P., Federoff, H.J. & Lim, S.T. Activity-dependent alpha-cleavage of nectin-1 is mediated by a disintegrin and metalloprotease 10 (ADAM10). 2010 J Biol Chem
    Vol. 285(30), pp. 22919-22926School: Neuroscience Department, Georgetown University Medical Center, Washington, D. C. 20057, USA. 
    DOI URL 
    Abstract: Nectin-1 is known to undergo ectodomain shedding by alpha-secretase
    and subsequent proteolytic processing by gamma-secretase. How secretase-mediated
    cleavage of nectin-1 is regulated in neuronal cells and how nectin-1
    cleavage affects synaptic adhesion is poorly understood. We have
    investigated alpha-and gamma-secretase-mediated processing of nectin-1
    in primary cortical neurons and identified which protease acts as
    a alpha-secretase. We report here that NMDA receptor activation,
    but not stimulation of AMPA or metabotropic glutamate receptors,
    resulted in robust alpha- and gamma-secretase cleavage of nectin-1
    in mature cortical neurons. Cleavage of nectin-1 required influx
    of Ca(2+) through the NMDA receptor, and activation of calmodulin,
    but was not dependent on calcium/calmodulin-dependent protein kinase
    II (CaMKII) activation. We found that ADAM10 is the major secretase
    responsible for nectin-1 ectodomain cleavage in neurons and the brain.
    These observations suggest that alpha- and gamma-secretase processing
    of nectin-1 is a Ca(2+)/calmodulin-regulated event that occurs under
    conditions of activity-dependent synaptic plasticity and ADAM10 and
    gamma-secretase are responsible for these cleavage events.
    BibTeX:
    @article{Kim2010,
      author = {Jinsook Kim and Christina Lilliehook and Amanda Dudak and Johannes Prox and Paul Saftig and Howard J Federoff and Seung T Lim},
      title = {Activity-dependent alpha-cleavage of nectin-1 is mediated by a disintegrin and metalloprotease 10 (ADAM10).},
      journal = {J Biol Chem},
      school = {Neuroscience Department, Georgetown University Medical Center, Washington, D. C. 20057, USA.},
      year = {2010},
      volume = {285},
      number = {30},
      pages = {22919--22926},
      url = {http://dx.doi.org/10.1074/jbc.M110.126649},
      doi = {http://doi.org/10.1074/jbc.M110.126649}
    }
    
    Lee, K.J., Moussa, C.E.H., Lee, Y., Sung, Y., Howell, B.W., Turner, R.S., Pak, D.T.S. & Hoe, H.S. Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines. 2010 Neuroscience
    Vol. 169(1), pp. 344-356School: Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Synapse loss induced by amyloid beta (Abeta) is thought to be a primary
    contributor to cognitive decline in Alzheimer's disease. Abeta is
    generated by proteolysis of amyloid precursor protein (APP), a synaptic
    receptor whose physiological function remains unclear. In the present
    study, we investigated the role of APP in dendritic spine formation,
    which is known to be important for learning and memory. We found
    that overexpression of APP increased spine number, whereas knockdown
    of APP reduced spine density in cultured hippocampal neurons. This
    spine-promoting effect of APP required both the extracellular and
    intracellular domains of APP, and was accompanied by specific upregulation
    of the GluR2, but not the GluR1, subunit of AMPA receptors. In an
    in vivo experiment, we found that cortical layers II/III and hippocampal
    CA1 pyramidal neurons in 1 year-old APP-deficient mice had fewer
    and shorter dendritic spines than wild-type littermates. In contrast,
    transgenic mice overexpressing mutant APP exhibited increased spine
    density compared to control animals, though only at a young age prior
    to overaccumulation of soluble amyloid. Additionally, increased glutamate
    synthesis was observed in young APP transgenic brains, whereas glutamate
    levels were decreased and GABA levels were increased in APP-deficient
    mice. These results demonstrate that APP is important for promoting
    spine formation and is required for proper spine development.
    BibTeX:
    @article{Lee2010,
      author = {Lee, K. J. and Moussa, C E H. and Lee, Y. and Sung, Y. and Howell, B. W. and Turner, R. S. and Pak, D T S. and Hoe, H. S.},
      title = {Beta amyloid-independent role of amyloid precursor protein in generation and maintenance of dendritic spines.},
      journal = {Neuroscience},
      school = {Department of Pharmacology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057-1464, USA.},
      year = {2010},
      volume = {169},
      number = {1},
      pages = {344--356},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2010.04.078},
      doi = {http://doi.org/10.1016/j.neuroscience.2010.04.078}
    }
    
    Lim, S.T., Airavaara, M. & Harvey, B.K. Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS. 2010 Pharmacol Res
    Vol. 61(1), pp. 14-26School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States. 
    DOI URL 
    Abstract: The clinical manifestation of most diseases of the central nervous
    system results from neuronal dysfunction or loss. Diseases such as
    stroke, epilepsy and neurodegeneration (e.g. Alzheimer's disease
    and Parkinson's disease) share common cellular and molecular mechanisms
    (e.g. oxidative stress, endoplasmic reticulum stress, mitochondrial
    dysfunction) that contribute to the loss of neuronal function. Neurotrophic
    factors (NTFs) are secreted proteins that regulate multiple aspects
    of neuronal development including neuronal maintenance, survival,
    axonal growth and synaptic plasticity. These properties of NTFs make
    them likely candidates for preventing neurodegeneration and promoting
    neuroregeneration. One approach to delivering NTFs to diseased cells
    is through viral vector-mediated gene delivery. Viral vectors are
    now routinely used as tools for studying gene function as well as
    developing gene-based therapies for a variety of diseases. Currently,
    many clinical trials using viral vectors in the nervous system are
    underway or completed, and seven of these trials involve NTFs for
    neurodegeneration. In this review, we discuss viral vector-mediated
    gene transfer of NTFs to treat neurodegenerative diseases of the
    central nervous system.
    BibTeX:
    @article{Lim2010,
      author = {Seung T Lim and Mikko Airavaara and Brandon K Harvey},
      title = {Viral vectors for neurotrophic factor delivery: a gene therapy approach for neurodegenerative diseases of the CNS.},
      journal = {Pharmacol Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, United States.},
      year = {2010},
      volume = {61},
      number = {1},
      pages = {14--26},
      url = {http://dx.doi.org/10.1016/j.phrs.2009.10.002},
      doi = {http://doi.org/10.1016/j.phrs.2009.10.002}
    }
    
    Maguire-Zeiss, K.A. & Federoff, H.J. Future directions for immune modulation in neurodegenerative disorders: focus on Parkinson's disease. 2010 J Neural Transm
    Vol. 117(8), pp. 1019-1025School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: One common feature of neurodegenerative diseases is neuroinflammation.
    In the case of Parkinson's disease (PD), neuroinflammation appears
    early and persists throughout the disease course. The principal cellular
    mediator of brain inflammation is the resident microglia which share
    many features with related hematopoietically derived macrophages.
    Microglia can become activated by misfolded proteins including the
    PD relevant example, alpha-synuclein, a presynaptic protein. When
    activated, microglia release pro-inflammatory diffusible mediators
    that promote dysfunction and contribute to the death of the PD vulnerable
    dopaminergic neurons in the midbrain. Recently, the orphan nuclear
    receptor Nurr1, well known as a critical determinant in dopaminergic
    neuron maturation, has been ascribed two new properties. First, it
    promotes the production and release of the neuropeptide vasoactive
    intestinal peptide that functions both to stimulate dopaminergic
    neuron survival and inhibit neuroinflammation. Second, Nurr1 suppresses
    the expression and release of pro-inflammatory cytokines in glial
    cells. Herein, we discuss these new findings in context of strategies
    to attenuate neuroinflammation in PD.
    BibTeX:
    @article{Maguire-Zeiss2010,
      author = {Kathleen A Maguire-Zeiss and Howard J Federoff},
      title = {Future directions for immune modulation in neurodegenerative disorders: focus on Parkinson's disease.},
      journal = {J Neural Transm},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2010},
      volume = {117},
      number = {8},
      pages = {1019--1025},
      url = {http://dx.doi.org/10.1007/s00702-010-0431-6},
      doi = {http://doi.org/10.1007/s00702-010-0431-6}
    }
    
    Minami, S.S., Cordova, A., Cirrito, J.R., Tesoriero, J.A., Babus, L.W., Davis, G.C., Dakshanamurthy, S., Turner, R.S., Pak, D.T., Rebeck, G.W., Paige, M. & Hoe, H.-S. ApoE mimetic peptide decreases Abeta production in vitro and in vivo. 2010 Mol Neurodegener
    Vol. 5, pp. 16School: Department of Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. map65@georgetown.edu. 
    DOI URL 
    Abstract: ABSTRACT:Apolipoprotein E (apoE) is postulated to affect brain Abeta
    levels through multiple mechanisms--by altering amyloid precursor
    protein (APP) processing, Abeta degradation, and Abeta clearance.
    We previously showed that an apoE-derived peptide containing a double
    repeat of the receptor-binding region was similarly effective in
    increasing APP processing in vivo. Here, we further examined whether
    peptides containing tandem repeats of the apoE receptor-binding region
    (amino acids 141-149) affected APP trafficking, APP processing, and
    Abeta production.We found that peptides containing a double or triple
    tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased
    cell surface APP and decreased Abeta levels in PS1-overexpressing
    PS70 cells and in primary neurons. This effect was potentiated by
    a sequential increase in the number of apoE receptor-binding domain
    repeats (trimer > dimer > monomer). We previously showed that the
    apoE dimer increased APP CTF in vivo; to determine whether the dimer
    also affected secreted APP or Abeta levels, we performed a single
    hippocampal injection of the apoE dimer in wild-type mice and analyzed
    its effect on APP processing. We found increased sAPPalpha and decreased
    Abeta levels at 24 hrs after treatment, suggesting that the apoE
    dimer may increase alpha-secretase cleavage.These data suggest that
    small peptides consisting of tandem repeats of the apoE receptor-binding
    region are sufficient to alter APP trafficking and processing. The
    potency of these peptides increased with increasing repeats of the
    receptor binding domain of apoE. In addition, in vivo administration
    of the apoE peptide (dimer) increased sAPPalpha and decreased Abeta
    levels in wild-type mice. Overall, these findings contribute to our
    understanding of the effects of apoE on APP processing and Abeta
    production both in vitro and in vivo.
    BibTeX:
    @article{Minami2010a,
      author = {S. Sakura Minami and Antoinette Cordova and John R Cirrito and Joseph A Tesoriero and Lenard W Babus and Gary C Davis and Sivanesan Dakshanamurthy and R. Scott Turner and Daniel Ts Pak and G. William Rebeck and Mikell Paige and Hyang-Sook Hoe},
      title = {ApoE mimetic peptide decreases Abeta production in vitro and in vivo.},
      journal = {Mol Neurodegener},
      school = {Department of Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. map65@georgetown.edu.},
      year = {2010},
      volume = {5},
      pages = {16},
      url = {http://dx.doi.org/10.1186/1750-1326-5-16},
      doi = {http://doi.org/10.1186/1750-1326-5-16}
    }
    
    Minami, S.S., Sidahmed, E., Aid, S., Shimoji, M., Niikura, T., Mocchetti, I., Rebeck, G.W., Prendergast, J.S., Dealwis, C., Wetzel, R., Bosetti, F., Matsuoka, Y., Hoe, H.-S. & Turner, R.S. Therapeutic versus neuroinflammatory effects of passive immunization is dependent on AΒ/amyloid burden in a transgenic mouse model of Alzheimer's disease. 2010 J Neuroinflammation
    Vol. 7, pp. 57School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Passive immunization with antibodies directed to AΒ decreases brain
    AΒ/amyloid burden and preserves memory in transgenic mouse models
    of Alzheimer's disease (AD). This therapeutic strategy is under intense
    scrutiny in clinical studies, but its application is limited by neuroinflammatory
    side effects (autoimmune encephalitis and vasogenic edema).We intravenously
    administered the monoclonal AΒ protofibril antibody PFA1 to aged
    (22 month) male and female 3 x tg AD mice with intermediate or advanced
    AD-like neuropathologies, respectively, and measured brain and serum
    AΒ and CNS cytokine levels. We also examined 17 month old 3 ? tg
    AD female mice with intermediate pathology to determine the effect
    of amyloid burden on responses to passive immunization.The 22 month
    old male mice immunized with PFA1 had decreased brain AΒ, increased
    serum AΒ, and no change in CNS cytokine levels. In contrast, 22 month
    old immunized female mice revealed no change in brain AΒ, decreased
    serum AΒ, and increased CNS cytokine levels. Identical experiments
    in younger (17 month old) female 3 ? tg AD mice with intermediate
    AD-like neuropathologies revealed a trend towards decreased brain
    AΒ and increased serum AΒ accompanied by a decrease in CNS MCP-1.These
    data suggest that passive immunization with PFA1 in 3 ? tg AD mice
    with intermediate disease burden, regardless of sex, is effective
    in mediating potentially therapeutic effects such as lowering brain
    AΒ. In contrast, passive immunization of mice with a more advanced
    amyloid burden may result in potentially adverse effects (encephalitis
    and vasogenic edema) mediated by certain proinflammatory cytokines.
    BibTeX:
    @article{Minami2010,
      author = {S. Sakura Minami and Elkhansa Sidahmed and Saba Aid and Mika Shimoji and Takako Niikura and Italo Mocchetti and G. William Rebeck and Jay S Prendergast and Chris Dealwis and Ronald Wetzel and Francesca Bosetti and Yasuji Matsuoka and Hyang-Sook Hoe and R. Scott Turner},
      title = {Therapeutic versus neuroinflammatory effects of passive immunization is dependent on AΒ/amyloid burden in a transgenic mouse model of Alzheimer's disease.},
      journal = {J Neuroinflammation},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20057, USA.},
      year = {2010},
      volume = {7},
      pages = {57},
      url = {http://dx.doi.org/10.1186/1742-2094-7-57},
      doi = {http://doi.org/10.1186/1742-2094-7-57}
    }
    
    N'Gouemo, P., Yasuda, R. & Faingold, C.L. Seizure susceptibility is associated with altered protein expression of voltage-gated calcium channel subunits in inferior colliculus neurons of the genetically epilepsy-prone rat. 2010 Brain Res
    Vol. 1308, pp. 153-157School: Department of Pediatrics and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. pn@georgetown.edu 
    DOI URL 
    Abstract: The inferior colliculus (IC) is the consensus site for seizure initiation
    in the genetically epilepsy-prone rat (GEPR). We have previously
    reported that the current density of high threshold voltage-activated
    (HVA) calcium (Ca(2+)) channels was markedly enhanced in IC neurons
    of the GEPR-3 (moderate seizure severity substrain of the GEPR).
    The present study examines whether subunit protein levels of HVA
    Ca(2+) channels are altered in IC neurons that exhibit enhanced Ca(2+)
    current density. Quantification shows that the levels of protein
    expression of the Ca(2+) channel pore-forming alpha1D (L-type) and
    alpha1E subunits (R-type) were significantly increased in IC neurons
    of seizure-naive GEPR-3s (SN-GEPR-3s) compared to control Sprague-Dawley
    (SD) rats. Significant increases and decreases in the levels of protein
    expression of Ca(2+) channel regulatory beta3 and alpha2delta subunits
    occurred in IC neurons of SN-GEPR-3s compared to control SD rats,
    respectively. No changes occurred in the protein expression of Ca(2+)
    channel pore-forming alpha1A (P/Q-type), alpha1B (N-type) and alpha1C
    (L-type) subunits in IC neurons of SN-GEPR-3s compared to control
    SD rats. A single seizure selectively enhanced protein expression
    of Ca(2+) channel alpha1A subunits in IC neurons of GEPR-3s. Thus,
    up-regulation of Ca(2+) channel alpha1D and alpha1E subunits may
    represent the molecular mechanisms for the enhanced current density
    of L- and R-type of HVA Ca(2+) channels in IC neurons of the GEPR,
    and may contribute to the genetic basis of their enhanced seizure
    susceptibility. The up-regulation of Ca(2+) channel alpha1A subunits
    induced by seizures may contribute to the increasing IC neuronal
    excitability that results from repetitive seizures in the GEPR.
    BibTeX:
    @article{N'Gouemo2010,
      author = {Prosper N'Gouemo and Robert Yasuda and Carl L Faingold},
      title = {Seizure susceptibility is associated with altered protein expression of voltage-gated calcium channel subunits in inferior colliculus neurons of the genetically epilepsy-prone rat.},
      journal = {Brain Res},
      school = {Department of Pediatrics and Interdisciplinary Program in Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. pn@georgetown.edu},
      year = {2010},
      volume = {1308},
      pages = {153--157},
      url = {http://dx.doi.org/10.1016/j.brainres.2009.10.019},
      doi = {http://doi.org/10.1016/j.brainres.2009.10.019}
    }
    
    Nemeth, D., Janacsek, K., Londe, Z., Ullman, M.T., Howard, D.V. & Howard, J.H. Sleep has no critical role in implicit motor sequence learning in young and old adults. 2010 Exp Brain Res
    Vol. 201(2), pp. 351-358School: Brain and Language Lab, Department of Neuroscience, Georgetown University, Washington, DC, USA. nemethd@edpsy.u-szeged.hu 
    DOI URL 
    Abstract: The influence of sleep on motor skill consolidation has been a research
    topic of increasing interest. In this study, we distinguished general
    skill learning from sequence-specific learning in a probabilistic
    implicit sequence learning task (alternating serial reaction time)
    in young and old adults before and after a 12-h offline interval
    which did or did not contain sleep (p.m.-a.m. and a.m.-p.m. groups,
    respectively). The results showed that general skill learning, as
    assessed via overall reaction time, improved offline in both the
    young and older groups, with the young group improving more than
    the old. However, the improvement was not sleep-dependent, in that
    there was no difference between the a.m.-p.m. and p.m.-a.m. groups.
    We did not find sequence-specific offline improvement in either age
    group for the a.m.-either p.m. or p.m.-a.m. groups, suggesting that
    consolidation of this kind of implicit motor sequence learning may
    not be influenced by sleep.
    BibTeX:
    @article{Nemeth2010,
      author = {Dezso Nemeth and Karolina Janacsek and Zsuzsa Londe and Michael T Ullman and Darlene V Howard and James H Howard},
      title = {Sleep has no critical role in implicit motor sequence learning in young and old adults.},
      journal = {Exp Brain Res},
      school = {Brain and Language Lab, Department of Neuroscience, Georgetown University, Washington, DC, USA. nemethd@edpsy.u-szeged.hu},
      year = {2010},
      volume = {201},
      number = {2},
      pages = {351--358},
      url = {http://dx.doi.org/10.1007/s00221-009-2024-x},
      doi = {http://doi.org/10.1007/s00221-009-2024-x}
    }
    
    Obleser, J., Leaver, A.M., Vanmeter, J. & Rauschecker, J.P. Segregation of vowels and consonants in human auditory cortex: evidence for distributed hierarchical organization. 2010 Front Psychol
    Vol. 1, pp. 232School: Laboratory of Integrative Neuroscience and Cognition, Department of Physiology and Biophysics, Georgetown University Medical Center Washington, DC, USA. 
    DOI URL 
    Abstract: The speech signal consists of a continuous stream of consonants and
    vowels, which must be de- and encoded in human auditory cortex to
    ensure the robust recognition and categorization of speech sounds.
    We used small-voxel functional magnetic resonance imaging to study
    information encoded in local brain activation patterns elicited by
    consonant-vowel syllables, and by a control set of noise bursts.
    First, activation of anterior-lateral superior temporal cortex was
    seen when controlling for unspecific acoustic processing (syllables
    versus band-passed noises, in a "classic" subtraction-based design).
    Second, a classifier algorithm, which was trained and tested iteratively
    on data from all subjects to discriminate local brain activation
    patterns, yielded separations of cortical patches discriminative
    of vowel category versus patches discriminative of stop-consonant
    category across the entire superior temporal cortex, yet with regional
    differences in average classification accuracy. Overlap (voxels correctly
    classifying both speech sound categories) was surprisingly sparse.
    Third, lending further plausibility to the results, classification
    of speech-noise differences was generally superior to speech-speech
    classifications, with the no exception of a left anterior region,
    where speech-speech classification accuracies were significantly
    better. These data demonstrate that acoustic-phonetic features are
    encoded in complex yet sparsely overlapping local patterns of neural
    activity distributed hierarchically across different regions of the
    auditory cortex. The redundancy apparent in these multiple patterns
    may partly explain the robustness of phonemic representations.
    BibTeX:
    @article{Obleser2010,
      author = {Obleser, Jonas and Leaver, Amber M. and Vanmeter, John and Rauschecker, Josef P.},
      title = {Segregation of vowels and consonants in human auditory cortex: evidence for distributed hierarchical organization.},
      journal = {Front Psychol},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Physiology and Biophysics, Georgetown University Medical Center Washington, DC, USA.},
      year = {2010},
      volume = {1},
      pages = {232},
      url = {http://dx.doi.org/10.3389/fpsyg.2010.00232},
      doi = {http://doi.org/10.3389/fpsyg.2010.00232}
    }
    
    Rauschecker, J.P., Leaver, A.M. & Mühlau, M. Tuning out the noise: limbic-auditory interactions in tinnitus. 2010 Neuron
    Vol. 66(6), pp. 819-826School: Laboratory of Integrative Neuroscience and Cognition, Georgetown University Medical Center, Washington, DC 20057-1460, USA. rauschej@georgetown.edu 
    DOI URL 
    Abstract: Tinnitus, the most common auditory disorder, affects about 40 million
    people in the United States alone, and its incidence is rising due
    to an aging population and increasing noise exposure. Although several
    approaches for the alleviation of tinnitus exist, there is as of
    yet no cure. The present article proposes a testable model for tinnitus
    that is grounded in recent findings from human imaging and focuses
    on brain areas in cortex, thalamus, and ventral striatum. Limbic
    and auditory brain areas are thought to interact at the thalamic
    level. While a tinnitus signal originates from lesion-induced plasticity
    of the auditory pathways, it can be tuned out by feedback connections
    from limbic regions, which block the tinnitus signal from reaching
    auditory cortex. If the limbic regions are compromised, this "noise-cancellation"
    mechanism breaks down, and chronic tinnitus results. Hopefully, this
    model will ultimately enable the development of effective treatment.
    BibTeX:
    @article{Rauschecker2010,
      author = {Josef P Rauschecker and Amber M Leaver and Mark Mühlau},
      title = {Tuning out the noise: limbic-auditory interactions in tinnitus.},
      journal = {Neuron},
      school = {Laboratory of Integrative Neuroscience and Cognition, Georgetown University Medical Center, Washington, DC 20057-1460, USA. rauschej@georgetown.edu},
      year = {2010},
      volume = {66},
      number = {6},
      pages = {819--826},
      url = {http://dx.doi.org/10.1016/j.neuron.2010.04.032},
      doi = {http://doi.org/10.1016/j.neuron.2010.04.032}
    }
    
    Rebeck, G.W., Hoe, H.-S. & Moussa, C.E.-H. Beta-amyloid1-42 gene transfer model exhibits intraneuronal amyloid, gliosis, tau phosphorylation, and neuronal loss. 2010 J Biol Chem
    Vol. 285(10), pp. 7440-7446School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Alzheimer disease is characterized by extracellular beta-amyloid (Abeta)
    plaques and intracellular inclusions containing neurofibrillary tangles
    of phospho-Tau and intraneuronal Abeta associated with neuronal cell
    death. We generated a novel gene transfer animal model using lentiviral
    Abeta(1-42) that resulted in intracellular but not extracellular
    Abeta accumulations in the targeted rat primary motor cortex. Expression
    of intracellular Abeta(1-42) led to pathological changes seen in
    human Alzheimer disease brains, including cell death, inflammatory
    signs, activation of two Tau kinases, and Tau hyperphosphorylation.
    Promoting clearance of lentiviral Abeta(1-42) reversed these effects,
    demonstrating that intraneuronal Abeta(1-42) is a toxic peptide that
    lies upstream of Tau modification. These studies reveal the role
    of intracellular Abeta(1-42) in a novel gene transfer animal model,
    which is a useful tool to study intraneuronal Abeta(1-42)-induced
    pathology in the absence of extracellular plaques. Targeted delivery
    of Abeta will allow speedy delineation of pathological mechanisms
    associated with specific neurodegenerative lesions.
    BibTeX:
    @article{Rebeck2010,
      author = {G. William Rebeck and Hyang-Sook Hoe and Charbel E-H Moussa},
      title = {Beta-amyloid1-42 gene transfer model exhibits intraneuronal amyloid, gliosis, tau phosphorylation, and neuronal loss.},
      journal = {J Biol Chem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2010},
      volume = {285},
      number = {10},
      pages = {7440--7446},
      url = {http://dx.doi.org/10.1074/jbc.M109.083915},
      doi = {http://doi.org/10.1074/jbc.M109.083915}
    }
    
    Verbalis, J.G. Brain volume regulation in response to changes in osmolality. 2010 Neuroscience
    Vol. 168(4), pp. 862-870School: Department of Medicine, 232 Building D, Georgetown University Medical Center, 4000 Reservoir Road NW, Washington, DC 20007, USA. verbalis@georgetown.edu 
    DOI URL 
    Abstract: Hypoosmolality and hyperosmolality are relatively common clinical
    problems. Many different factors contribute to the substantial morbidity
    and mortality known to occur during states of altered osmotic homeostasis.
    The brain is particularly vulnerable to disturbances of body fluid
    osmolality. The most serious complications are associated with pathological
    changes in brain volume: brain edema during hypoosmolar states and
    brain dehydration during hyperosmolar states. Studies in animals
    have elucidated many of the mechanisms involved with brain adaptation
    to osmotic stresses, and indicate that it is a complex process involving
    transient changes in water content and sustained changes in electrolyte
    and organic osmolyte contents. Appreciation of the nature of the
    adaptation process, and conversely the deadaptation processes that
    occur after recovery from hypoosmolality and hyperosmolality, enables
    a better understanding of the marked variations in neurological sequelae
    that characterize hyperosmolar and hypoosmolar states, and provides
    a basis for more rational therapies.
    BibTeX:
    @article{Verbalis2010,
      author = {Verbalis, J. G.},
      title = {Brain volume regulation in response to changes in osmolality.},
      journal = {Neuroscience},
      school = {Department of Medicine, 232 Building D, Georgetown University Medical Center, 4000 Reservoir Road NW, Washington, DC 20007, USA. verbalis@georgetown.edu},
      year = {2010},
      volume = {168},
      number = {4},
      pages = {862--870},
      url = {http://dx.doi.org/10.1016/j.neuroscience.2010.03.042},
      doi = {http://doi.org/10.1016/j.neuroscience.2010.03.042}
    }
    
    Wu, J., Wrathall, J.R. & Schachner, M. Phosphatidylinositol 3-kinase/protein kinase Cdelta activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes. 2010 Glia
    Vol. 58(3), pp. 315-328School: W. M. Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University in the State of New Jersey, 604 Allison Road, Piscataway, NJ 08854, USA. jw365@georgetown.edu 
    DOI URL 
    Abstract: Upregulation of expression of the close homolog of adhesion molecule
    L1 (CHL1) by reactive astrocytes in the glial scar reduces axonal
    regeneration and inhibits functional recovery after spinal cord injury
    (SCI). Here, we investigate the molecular mechanisms underlying upregulation
    of CHL1 expression by analyzing the signal transduction pathways
    in vitro. We show that astrogliosis stimulated by bacterial lipopolysaccharide
    (LPS) upregulates CHL1 expression in primary cultures of mouse cerebral
    astrocytes, coinciding with elevated protein synthesis and translocation
    of protein kinase delta (PKCdelta) from cytosol to the membrane fraction.
    Blocking PKCdelta activity pharmacologically and genetically attenuates
    LPS-induced elevation of CHL1 protein expression through a phosphatidylinositol
    3-kinase (PI3K) dependent pathway. LPS induces extracellular signal-regulated
    kinases (ERK1/2) phosphorylation through PKCdelta and blockade of
    ERK1/2 activation abolishes upregulation of CHL1 expression. LPS-triggered
    upregulation of CHL1 expression mediated through translocation of
    nuclear factor kappaB (NF-kappaB) to the nucleus is blocked by a
    specific NF-kappaB inhibitor and by inhibition of PI3K, PKCdelta,
    and ERK1/2 activities, implicating NF-kappaB as a downstream target
    for upregulation of CHL1 expression. Furthermore, the LPS-mediated
    upregulation of CHL1 expression by reactive astrocytes is inhibitory
    for hippocampal neurite outgrowth in cocultures. Although the LPS-triggered
    NO-guanylate cyclase-cGMP pathway upregulates glial fibrillary acid
    protein expression in cultured astrocytes, we did not observe this
    pathway to mediate LPS-induced upregulation of CHL1 expression. Our
    results indicate that elevated CHL1 expression by reactive astrocytes
    requires activation of PI3K/PKCdelta-dependent pathways and suggest
    that reduction of PI3K/PKCdelta activity represents a therapeutic
    target to downregulate CHL1 expression and thus benefit axonal regeneration
    after SCI.
    BibTeX:
    @article{Wu2010a,
      author = {Junfang Wu and Jean R Wrathall and Melitta Schachner},
      title = {Phosphatidylinositol 3-kinase/protein kinase Cdelta activation induces close homolog of adhesion molecule L1 (CHL1) expression in cultured astrocytes.},
      journal = {Glia},
      school = {W. M. Keck Center for Collaborative Neuroscience, Department of Cell Biology and Neuroscience, Rutgers University in the State of New Jersey, 604 Allison Road, Piscataway, NJ 08854, USA. jw365@georgetown.edu},
      year = {2010},
      volume = {58},
      number = {3},
      pages = {315--328},
      url = {http://dx.doi.org/10.1002/glia.20925},
      doi = {http://doi.org/10.1002/glia.20925}
    }
    
    Wu, J., Yoo, S., Wilcock, D., Lytle, J.M., Leung, P.Y., Colton, C.A. & Wrathall, J.R. Interaction of NG2(+) glial progenitors and microglia/macrophages from the injured spinal cord. 2010 Glia
    Vol. 58(4), pp. 410-422School: Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: Spinal cord contusion produces a central lesion surrounded by a peripheral
    rim of residual white matter. Despite stimulation of NG2(+) progenitor
    cell proliferation, the lesion remains devoid of normal glia chronically
    after spinal cord injury (SCI). To investigate potential cell-cell
    interactions of the predominant cells in the lesion at 3 days after
    injury, we used magnetic activated cell sorting to purify NG2(+)
    progenitors and OX42(+) microglia/macrophages from contused rat spinal
    cord. Purified NG2(+) cells from the injured cord grew into spherical
    masses when cultured in defined medium with FGF2 plus GGF2. The purified
    OX42(+) cells did not form spheroids and significantly reduced sphere
    growth by NG2(+) cells in co-cultures. Conditioned medium from these
    OX42(+) cells, unlike that from normal peritoneal macrophages or
    astrocytes also inhibited growth of NG2(+) cells, suggesting inhibition
    by secreted factors. Expression analysis of freshly purified OX42(+)
    cells for a panel of six genes for secreted factors showed expression
    of several that could contribute to inhibition of NG2(+) cells. Further,
    the pattern of expression of four of these, TNFalpha, TSP1, TIMP1,
    MMP9, in sequential coronal tissue segments from a 2 cm length of
    cord centered on the injury epicenter correlated with the expression
    of Iba1, a marker gene for OX42(+) cells, strongly suggesting a potential
    regional influence by activated microglia/macrophages on NG2(+) cells
    in vivo after SCI. Thus, the nonreplacement of lost glial cells in
    the central lesion zone may involve, at least in part, inhibitory
    factors produced by microglia/macrophages that are concentrated within
    the lesion.
    BibTeX:
    @article{Wu2010,
      author = {Junfang Wu and Soonmoon Yoo and Donna Wilcock and Judith M Lytle and Philberta Y Leung and Carol A Colton and Jean R Wrathall},
      title = {Interaction of NG2(+) glial progenitors and microglia/macrophages from the injured spinal cord.},
      journal = {Glia},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA.},
      year = {2010},
      volume = {58},
      number = {4},
      pages = {410--422},
      url = {http://dx.doi.org/10.1002/glia.20932},
      doi = {http://doi.org/10.1002/glia.20932}
    }
    
    Yakovlev, A., Khafizova, M., Abdullaev, Z., Loukinov, D. & Kondratyev, A. Epigenetic regulation of caspase-3 gene expression in rat brain development. 2010 Gene
    Vol. 450(1-2), pp. 103-108School: Department of Neuroscience, Georgetown University, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: The expression levels of caspase-3, a major contributor to the execution
    of neuronal apoptosis, markedly decrease in the process of brain
    maturation. We have previously cloned the rat caspase-3 gene promoter
    and identified its essential regulatory elements. In the present
    study, we extended previous findings by examining transcriptional
    regulation of caspase-3 expression in the rat brain of two different
    ages, corresponding to the immature and mature brain. In particular,
    we determined that the rate of transcription initiation substantially
    declines during brain maturation. Furthermore, we established that
    mRNA levels of Ets1, Ets2, and Sp1 do not change in the brain with
    maturation, suggesting that these transcription factors do not contribute
    to age-dependent caspase-3 down-regulation. Hence, we examined a
    role of DNA methylation and histone modification in this process.
    Utilizing bisulfite DNA sequencing, we determined the presence of
    age-dependent differentially methylated fragments within the caspase-3
    promoter region. Strikingly, differentially methylated CpG sites
    correspond to the predicted binding sites for a number of transcription
    factors that have been previously shown to be involved in neuronal
    development and differentiation. Moreover, using chromatin immunoprecipitation,
    we found that mature brains displayed significantly lower levels
    of histone 3 acetylated Lys14 and histone 4 acetylated Lys5, 8, 12,
    and 16. This observation is consistent with the decreased level of
    expression of caspase-3 in the mature brain. Together with our observation
    that histone deacetylase inhibitor, trichostatin A, increased the
    level of caspase-3 mRNA in cortical neurons in vitro, these results
    further indicate an important role of epigenetic factors in the regulation
    of caspase-3 gene expression.
    BibTeX:
    @article{Yakovlev2010,
      author = {Alexander Yakovlev and Maryam Khafizova and Ziedulla Abdullaev and Dmitri Loukinov and Alexei Kondratyev},
      title = {Epigenetic regulation of caspase-3 gene expression in rat brain development.},
      journal = {Gene},
      school = {Department of Neuroscience, Georgetown University, Washington, DC 20057, USA.},
      year = {2010},
      volume = {450},
      number = {1-2},
      pages = {103--108},
      url = {http://dx.doi.org/10.1016/j.gene.2009.10.008},
      doi = {http://doi.org/10.1016/j.gene.2009.10.008}
    }
    
    Ahmed, F., MacArthur, L., Bernardi, M.A.D. & Mocchetti, I. Retrograde and anterograde transport of HIV protein gp120 in the nervous system. 2009 Brain Behav Immun
    Vol. 23(3), pp. 355-364School: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Neurodegeneration and gliosis are prominent pathological features
    of subjects with human immunodeficiency virus (HIV) dementia complex
    (HAD). In these patients, neurodegeneration occurs in uninfected
    neurons. In addition, these patients develop sensory neuropathy despite
    the antiretroviral therapy. The HIV protein gp120, which mimics some
    of the pathological alterations seen in HAD, is retrogradely transported
    in rodent neurons. However, it is still unclear whether gp120 can
    also be transported anterogradely and whether axonal transport can
    occur in the peripheral nervous system (PNS). To determine whether
    gp120 is transported retrogradely and/or anterogradely, we injected
    gp120IIIB together with the retrograde tracer fluoro-ruby (FR) or
    the anterograde tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine
    perchlorate (DiI) into the rat superior colliculi. We discovered
    that gp120 is retrogradely transported with FR along a direct pathway
    from the superior colliculus to the retina and anterogradely transported
    with DiI to several areas of the occipital cortex. To determine whether
    gp120 is also axonally transported in the peripheral nerves, gp120
    and FR were injected into the sciatic nerve. No gp120 immunoreactivity
    was found in the sciatic nerve or dorsal root ganglia, suggesting
    that gp120 axonal transport does not occur in the PNS. Gp120 axonal
    transport may play a role in neuronal injury. Therefore, we examined
    apoptosis at various time points after gp120 injection. Activated
    caspase-3 was evident within neurons transporting gp120. These results
    indicate that axonal transport of gp120 might exacerbate the pathogenesis
    of HIV-1.
    BibTeX:
    @article{Ahmed2009,
      author = {Farid Ahmed and Linda MacArthur and Maria A De Bernardi and Italo Mocchetti},
      title = {Retrograde and anterograde transport of HIV protein gp120 in the nervous system.},
      journal = {Brain Behav Immun},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04 Box 571464, 3970 Reservoir Rd, NW, Washington, DC 20057, USA.},
      year = {2009},
      volume = {23},
      number = {3},
      pages = {355--364},
      url = {http://dx.doi.org/10.1016/j.bbi.2008.11.007},
      doi = {http://doi.org/10.1016/j.bbi.2008.11.007}
    }
    
    Bachis, A., Biggio, F., Major, E.O. & Mocchetti, I. M- and T-tropic HIVs promote apoptosis in rat neurons. 2009 J Neuroimmune Pharmacol
    Vol. 4(1), pp. 150-160School: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, Box 571464, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Neuronal loss, reactive astrocytes, and other abnormalities are seen
    in the brain of individuals with acquired immune deficiency syndrome-associated
    Dementia Complex (ADC). Human immunodeficiency virus-1 (HIV-1) is
    believed to be the main agent causing ADC. However, little is known
    about the molecular and cellular mechanisms of HIV-1 neurotoxicity
    considering that HIV-1 does not infect post-mitotic neurons and that
    viral load does not necessarily correlate with ADC. Various viral
    proteins, such as the envelope protein gp120 and the transcription
    activator Tat, have been shown to induce neuronal apoptosis through
    direct and indirect mechanisms both in vitro and in vivo. Progeny
    HIV-1 virions can also cause neuronal death. However, it has not
    been fully established yet whether HIV-1 promotes neuronal apoptosis
    by a direct mechanism. To explore the neurotoxic effect of HIV-1,
    we exposed rat cerebellar granule cells and cortical neurons in culture
    to two different strains of HIV-1, IIIB and BaL, T- and M-tropic
    strains that utilize CXCR4 and CCR5 coreceptors, respectively, to
    infect cells. We observed that both viruses elicit a time-dependent
    apoptotic cell death in these cultures without inducing a productive
    infection as determined by the absence of the core protein of HIV-1,
    p24, in cell lysates. Instead, neurons were gp120 positive, suggesting
    that the envelope protein is shed by the virus and then subsequently
    internalized by neurons. The CXCR4 receptor antagonist AMD3100 or
    the CCR5 receptor inhibitor D-Ala-peptide T-amide blocked HIV IIIB
    and HIV Bal neurotoxicity, respectively. In contrast, the N-methyl-D-aspartate
    receptor blocker MK801 failed to protect neurons from HIV-mediated
    apoptosis, suggesting that HIV-1 neurotoxicity can be initiated by
    the viral protein gp120 binding to neuronal chemokine receptors.
    BibTeX:
    @article{Bachis2009,
      author = {Alessia Bachis and Francesca Biggio and Eugene O Major and Italo Mocchetti},
      title = {M- and T-tropic HIVs promote apoptosis in rat neurons.},
      journal = {J Neuroimmune Pharmacol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, Box 571464, Washington, DC 20057, USA.},
      year = {2009},
      volume = {4},
      number = {1},
      pages = {150--160},
      url = {http://dx.doi.org/10.1007/s11481-008-9141-3},
      doi = {http://doi.org/10.1007/s11481-008-9141-3}
    }
    
    Bhatt, S., Mbwana, J., Adeyemo, A., Sawyer, A., Hailu, A. & Vanmeter, J. Lying about facial recognition: an fMRI study. 2009 Brain Cogn
    Vol. 69(2), pp. 382-390School: ISIS Center, Georgetown University Medical Center, Box 571479, WA, DC 20057-1479, USA. sbb2@georgetown.edu 
    DOI URL 
    Abstract: Novel deception detection techniques have been in creation for centuries.
    Functional magnetic resonance imaging (fMRI) is a neuroscience technology
    that non-invasively measures brain activity associated with behavior
    and cognition. A number of investigators have explored the utilization
    and efficiency of fMRI in deception detection. In this study, 18
    subjects were instructed during an fMRI "line-up" task to either
    conceal (lie) or reveal (truth) the identities of individuals seen
    in study sets in order to determine the neural correlates of intentionally
    misidentifying previously known faces (lying about recognition).
    A repeated measures ANOVA (lie vs. truth and familiar vs. unfamiliar)
    and two paired t-tests (familiar vs. unfamiliar and familiar lie
    vs. familiar truth) revealed areas of activation associated with
    deception in the right MGF, red nucleus, IFG, SMG, SFG (with ACC),
    DLPFC, and bilateral precuneus. The areas activated in the present
    study may be involved in the suppression of truth, working and visuospatial
    memories, and imagery when providing misleading (deceptive) responses
    to facial identification prompts in the form of a "line-up".
    BibTeX:
    @article{Bhatt2009,
      author = {Bhatt, S. and Mbwana, J. and Adeyemo, A. and Sawyer, A. and Hailu, A. and Vanmeter, J.},
      title = {Lying about facial recognition: an fMRI study.},
      journal = {Brain Cogn},
      school = {ISIS Center, Georgetown University Medical Center, Box 571479, WA, DC 20057-1479, USA. sbb2@georgetown.edu},
      year = {2009},
      volume = {69},
      number = {2},
      pages = {382--390},
      url = {http://dx.doi.org/10.1016/j.bandc.2008.08.033},
      doi = {http://doi.org/10.1016/j.bandc.2008.08.033}
    }
    
    Burns, M.P., Zhang, L., Rebeck, G.W., Querfurth, H.W. & Moussa, C.E.-H. Parkin promotes intracellular Abeta1-42 clearance. 2009 Hum Mol Genet
    Vol. 18(17), pp. 3206-3216School: Department of Neuroscience, Georgetown University School of Medicine, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Alzheimer's disease and Parkinson's disease are common neurodegenerative
    diseases that may share some underlying mechanisms of pathogenesis.
    Abeta(1-42) fragments are found intracellularly, and extracellularly
    as amyloid plaques, in Alzheimer's disease and in dementia with Lewy
    Bodies. Parkin is an E3-ubiquitin ligase involved in proteasomal
    degradation of intracellular proteins. Mutations in parkin, which
    result in loss of parkin function, lead to early onset Parkinsonism.
    Here we tested whether the ubiquitin ligase activity of parkin could
    lead to reduction in intracellular human Abeta(1-42). Lentiviral
    constructs encoding either human parkin or human Abeta(1-42) were
    used to infect M17 neuroblastoma cells. Parkin expression resulted
    in reduction of intracellular human Abeta(1-42) levels and protected
    against its toxicity in M17 cells. Co-injection of lentiviral constructs
    into control rat primary motor cortex demonstrated that parkin co-expression
    reduced human Abeta(1-42) levels and Abeta(1-42)-induced neuronal
    degeneration in vivo. Parkin increased proteasomal activity, and
    proteasomal inhibition blocked the effects of parkin on reducing
    Abeta(1-42) levels. Incubation of Abeta(1-42) cell lysates with ubiquitin,
    in the presence of parkin, demonstrated the generation of Abeta-ubiquitin
    complexes. These data indicate that parkin promotes ubiquitination
    and proteasomal degradation of intracellular Abeta(1-42) and demonstrate
    a protective effect in neurodegenerative diseases with Abeta deposits.
    BibTeX:
    @article{Burns2009,
      author = {Mark P Burns and Lihua Zhang and G. William Rebeck and Henry W Querfurth and Charbel E-H Moussa},
      title = {Parkin promotes intracellular Abeta1-42 clearance.},
      journal = {Hum Mol Genet},
      school = {Department of Neuroscience, Georgetown University School of Medicine, Washington, DC 20057, USA.},
      year = {2009},
      volume = {18},
      number = {17},
      pages = {3206--3216},
      url = {http://dx.doi.org/10.1093/hmg/ddp258},
      doi = {http://doi.org/10.1093/hmg/ddp258}
    }
    
    Byrnes, K.R., Loane, D.J. & Faden, A.I. Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders. 2009 Neurotherapeutics
    Vol. 6(1), pp. 94-107School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. krb27@georgetown.edu 
    DOI URL 
    Abstract: Glutamate is a major excitatory neurotransmitter in the CNS that is
    involved in numerous cellular functions, including cell death and
    survival. Metabotropic glutamate receptors (mGluR) are G-protein
    coupled receptors that have been classified into three groups on
    the basis of signal transduction pathways and pharmacological profiles.
    Group I, II, and III mGluRs are found on cell types within and peripheral
    to the CNS, including neurons, microglia, astrocytes, oligodendrocytes,
    T- and B-cell lymphocytes, osteoblasts, hepatocytes, and endothelial
    cells, among others. These receptors have a number of effects on
    cells that can influence outcome after trauma, including reducing
    neuronal and oligodendroglial cell death, inflammation, and endothelial
    permeability. Thus, mGluRs are a promising multipotential therapeutic
    approach. Because the pathology of CNS trauma and neurodegeneration
    is multifactorial (including, for example, oxidative stress, mitochondrial
    breakdown, and inflammation), therapies that serve to modulate multiple
    pathophysiological pathways may prove more effective than those directed
    at a single target. This review examines the multipotential therapeutic
    utility of mGluR modulation in acute and chronic injury and neurodegeneration.
    BibTeX:
    @article{Byrnes2009a,
      author = {Kimberly R Byrnes and David J Loane and Alan I Faden},
      title = {Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.},
      journal = {Neurotherapeutics},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. krb27@georgetown.edu},
      year = {2009},
      volume = {6},
      number = {1},
      pages = {94--107},
      url = {http://dx.doi.org/10.1016/j.nurt.2008.10.038},
      doi = {http://doi.org/10.1016/j.nurt.2008.10.038}
    }
    
    Byrnes, K.R., Stoica, B., Loane, D.J., Riccio, A., Davis, M.I. & Faden, A.I. Metabotropic glutamate receptor 5 activation inhibits microglial associated inflammation and neurotoxicity. 2009 Glia
    Vol. 57(5), pp. 550-560School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road N.W., Washington, DC 20057, USA. krb27@georgetown.edu 
    DOI URL 
    Abstract: The Group I metabotropic glutamate receptor 5 (mGluR5) can modulate
    addiction, pain, and neuronal cell death. Expression of some mGluRs,
    such as Group II and III mGluRs, has been reported in microglia and
    may affect their activation. However, the expression and role of
    mGluR5 in microglia is unclear. Using immunocytochemistry and Western
    blot, we demonstrate that mGluR5 protein is expressed in primary
    microglial cultures. Activation of mGluR5 using the selective agonist
    (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) significantly reduces
    microglial activation in response to lipopolysaccharide, as indicated
    by a reduction in nitric oxide, reactive oxygen species, and TNFalpha
    production. Microglial induced neurotoxicity is also markedly reduced
    by CHPG treatment. The anti-inflammatory effects of CHPG are not
    observed in microglial cultures from mGluR5 knockout mice and are
    blocked by selective mGluR5 antagonists, suggesting that these actions
    are mediated by the mGluR5 receptor. Anti-inflammatory actions of
    mGluR5 activation are attenuated by phospholipase C and protein kinase
    C inhibitors, as well as by calcium chelators, suggesting that the
    mGluR5 activation in microglia involves the G(alphaq)-protein signal
    transduction pathway. These data indicate that microglial mGluR5
    may represent a novel target for modulating neuroinflammation, an
    important component of both acute and chronic neurodegenerative disorders.
    BibTeX:
    @article{Byrnes2009b,
      author = {Kimberly R Byrnes and Bogdan Stoica and David J Loane and Angela Riccio and Margaret I Davis and Alan I Faden},
      title = {Metabotropic glutamate receptor 5 activation inhibits microglial associated inflammation and neurotoxicity.},
      journal = {Glia},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road N.W., Washington, DC 20057, USA. krb27@georgetown.edu},
      year = {2009},
      volume = {57},
      number = {5},
      pages = {550--560},
      url = {http://dx.doi.org/10.1002/glia.20783},
      doi = {http://doi.org/10.1002/glia.20783}
    }
    
    Byrnes, K.R., Stoica, B., Riccio, A., Pajoohesh-Ganji, A., Loane, D.J. & Faden, A.I. Activation of metabotropic glutamate receptor 5 improves recovery after spinal cord injury in rodents. 2009 Ann Neurol
    Vol. 66(1), pp. 63-74School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. krb27@georgetown.edu 
    DOI URL 
    Abstract: Activation of metabotropic glutamate receptor 5 (mGluR5) has neuroprotective
    properties in vitro and has been reported to limit postischemic lesion
    volume in vivo. Previously, mGluR5 has been identified on microglia
    in vitro, but the effects of mGluR5 activation on inflammation in
    vivo or on recovery after spinal cord injury is unknown.Rats received
    intrathecal infusion of the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine
    (CHPG) for 7 days after moderate impact spinal cord injury at T9.
    Complementary studies examined CHPG effects on activated spinal microglia
    cultures.Functional motor recovery was significantly increased by
    CHPG treatment up to 28 days after injury, with improvements in weight
    bearing, step taking, and coordination of stepping behavior. CHPG
    treatment significantly reduced lesion volume and increased white
    matter sparing at 28 days after injury. Administration of CHPG attenuated
    microglial-associated inflammatory responses in a dose-dependent
    fashion, including expression of ED1, Iba-1, Galectin-3, NADPH oxidase
    components, tumor necrosis factor-alpha, and inducible nitric oxide
    synthase. Because mGluR5 is expressed by microglial cells in the
    rat spinal cord, such effects may be mediated by direct action on
    microglial cells. mGluR5 stimulation also reduced microglial activation
    and decreased microglial-induced neurotoxicity in spinal cord microglia
    cultures; the latter effects were blocked by the selective mGluR5
    antagonist MTEP.These data demonstrate that mGluR5 activation can
    reduce microglial-associated inflammation, suggesting that the protective
    effects of mGluR5 agonists may reflect this action. Ann Neurol 2009;66:63-74.
    BibTeX:
    @article{Byrnes2009,
      author = {Kimberly R Byrnes and Bogdan Stoica and Angela Riccio and Ahdeah Pajoohesh-Ganji and David J Loane and Alan I Faden},
      title = {Activation of metabotropic glutamate receptor 5 improves recovery after spinal cord injury in rodents.},
      journal = {Ann Neurol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. krb27@georgetown.edu},
      year = {2009},
      volume = {66},
      number = {1},
      pages = {63--74},
      url = {http://dx.doi.org/10.1002/ana.21673},
      doi = {http://doi.org/10.1002/ana.21673}
    }
    
    Dai, H., MacArthur, L., McAtee, M., Hockenbury, N., Tidwell, J.L., McHugh, B., Mansfield, K., Finn, T., Hamers, F.P.T. & Bregman, B.S. Activity-based therapies to promote forelimb use after a cervical spinal cord injury. 2009 J Neurotrauma
    Vol. 26(10), pp. 1719-1732School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Significant interest exists in strategies for improving forelimb function
    following spinal cord injury. We investigated the effect of enriched
    housing combined with skilled training on the recovery of skilled
    and automatic forelimb function after a cervical spinal cord injury
    in adult rats. All animals were pretrained in skilled reaching, gridwalk
    crossing, and overground locomotion. Some received a cervical over-hemisection
    lesion at C4-5, interrupting the right side of the spinal cord and
    dorsal columns bilaterally, and were housed in standard housing alone
    or enriched environments with daily training. A subset of animals
    received rolipram to promote neuronal plasticity. Animals were tested
    weekly for 4 weeks to measure reaching, errors on the gridwalk, locomotion,
    and vertical exploration. Biotinylated dextran amine was injected
    into the cortex to label the corticospinal tract. Enriched environments/daily
    training significantly increased the number and success of left reaches
    compared to standard housing. Animals also made fewer errors on the
    gridwalk, a measure of coordinated forelimb function. However, there
    were no significant improvements in forelimb use during vertical
    exploration or locomotion. Likewise, rolipram did not improve any
    of the behaviors tested. Both enriched housing and rolipram increased
    plasticity of the corticospinal tract rostral to the lesion. These
    studies indicate that skilled training after a cervical spinal cord
    injury improves recovery of skilled forelimb use (reaching) and coordinated
    limb function (gridwalk) but does not improve automatic forelimb
    function (locomotion and vertical exploration). These studies suggest
    that rehabilitating forelimb function after spinal cord injury will
    require separate strategies for descending and segmental pathways.
    BibTeX:
    @article{Dai2009,
      author = {Haining Dai and Linda MacArthur and Marietta McAtee and Nicole Hockenbury and J. Lille Tidwell and Brian McHugh and Kevin Mansfield and Tom Finn and Frank P T Hamers and Barbara S Bregman},
      title = {Activity-based therapies to promote forelimb use after a cervical spinal cord injury.},
      journal = {J Neurotrauma},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2009},
      volume = {26},
      number = {10},
      pages = {1719--1732},
      url = {http://dx.doi.org/10.1089/neu.2008-0592},
      doi = {http://doi.org/10.1089/neu.2008-0592}
    }
    
    Dumanis, S.B., Tesoriero, J.A., Babus, L.W., Nguyen, M.T., Trotter, J.H., Ladu, M.J., Weeber, E.J., Turner, R.S., Xu, B., Rebeck, G.W. & Hoe, H.-S. ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo. 2009 J Neurosci
    Vol. 29(48), pp. 15317-15322School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: The three human alleles of apolipoprotein E (APOE) differentially
    influence outcome after CNS injury and affect one's risk of developing
    Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute
    to various AD-related pathological changes (e.g., amyloid plaques
    and synaptic and neuron loss). Here, we systematically examined whether
    apoE isoforms (E2, E3, E4) exhibit differential effects on dendritic
    spine density and morphology in APOE targeted replacement (TR) mice,
    which lack AD pathological changes. Using Golgi staining, we found
    age-dependent effects of APOE4 on spine density in the cortex. The
    APOE4 TR mice had significantly reduced spine density at three independent
    time points (4 weeks, 3 months, and 1 year, 27.7% +/- 7.4 24.4br> +/- 8.6 and 55.6% +/- 10.5 respectively) compared with APOE3
    TR mice and APOE2 TR mice. Additionally, in APOE4 TR mice, shorter
    spines were evident compared with other APOE TR mice at 1 year. APOE2
    TR mice exhibited longer spines as well as significantly increased
    apical dendritic arborization in the cortex compared with APOE4 and
    APOE3 TR mice at 4 weeks. However, there were no differences in spine
    density across APOE genotypes in hippocampus. These findings demonstrate
    that apoE isoforms differentially affect dendritic complexity and
    spine formation, suggesting a role for APOE genotypes not only in
    acute and chronic brain injuries including AD, but also in normal
    brain functions.
    BibTeX:
    @article{Dumanis2009,
      author = {Sonya B Dumanis and Joseph A Tesoriero and Lenard W Babus and Madeline T Nguyen and Justin H Trotter and Mary Jo Ladu and Edwin J Weeber and R. Scott Turner and Baoji Xu and G. William Rebeck and Hyang-Sook Hoe},
      title = {ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo.},
      journal = {J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2009},
      volume = {29},
      number = {48},
      pages = {15317--15322},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.4026-09.2009},
      doi = {http://doi.org/10.1523/JNEUROSCI.4026-09.2009}
    }
    
    Glezer, L.S., Jiang, X. & Riesenhuber, M. Evidence for highly selective neuronal tuning to whole words in the "visual word form area". 2009 Neuron
    Vol. 62(2), pp. 199-204School: Department of Neuroscience, Georgetown University Medical Center, Research Building Room WP-12, 3970 Reservoir Road NW, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: Theories of reading have posited the existence of a neural representation
    coding for whole real words (i.e., an orthographic lexicon), but
    experimental support for such a representation has proved elusive.
    Using fMRI rapid adaptation techniques, we provide evidence that
    the human left ventral occipitotemporal cortex (specifically the
    "visual word form area," VWFA) contains a representation based on
    neurons highly selective for individual real words, in contrast to
    current theories that posit a sublexical representation in the VWFA.
    BibTeX:
    @article{Glezer2009,
      author = {Laurie S Glezer and Xiong Jiang and Maximilian Riesenhuber},
      title = {Evidence for highly selective neuronal tuning to whole words in the "visual word form area".},
      journal = {Neuron},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building Room WP-12, 3970 Reservoir Road NW, Washington, DC 20007, USA.},
      year = {2009},
      volume = {62},
      number = {2},
      pages = {199--204},
      url = {http://dx.doi.org/10.1016/j.neuron.2009.03.017},
      doi = {http://doi.org/10.1016/j.neuron.2009.03.017}
    }
    
    Herman, M.A., Cruz, M.T., Sahibzada, N., Verbalis, J. & Gillis, R.A. GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit. 2009 Am J Physiol Gastrointest Liver Physiol
    Vol. 296(1), pp. G101-G111School: Interdisciplinary Program in Neuroscience, Georgetown Univ. Medical Center, 3900 Reservoir Rd., NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: It has been proposed that there is an "apparent monosynaptic" connection
    between gastric vagal afferent nerve terminals and inhibitory projection
    neurons in the nucleus tractus solitarius (NTS) and that two efferent
    parallel pathways from the dorsal motor nucleus of the vagus (DMV)
    influence peripheral organs associated with these reflexes (6). The
    purpose of our study was to verify the validity of these views as
    they relate to basal control of gastric motility. To test the validity
    of a direct connection of vagal afferent terminals (known to release
    l-glutamate) directly impacting second-order projection neurons,
    we evaluated the effect of GABA(A) receptor blockade in the area
    of the medial subnucleus of the tractus solitarius (mNTS) on gastric
    motility. Microinjection of bicuculline methiodide into the mNTS
    produced robust decreases in gastric motility (-1.6 +/- 0.2 mmHg,
    P < 0.05, n = 23), which were prevented by cervical vagotomy and
    by pretreatment with kynurenic acid microinjected into the mNTS.
    Kynurenic acid per se had no effect on gastric motility. However,
    after GABA(A) receptor blockade in the mNTS, kynurenic acid produced
    a robust increase in gastric motility. To test for the contribution
    of two parallel efferent DMV pathways, we assessed the effect of
    either intravenous atropine methylbromide or N(G)-nitro-l-arginine
    methyl ester on baseline motility and on decreases in gastric motility
    induced by GABA(A) receptor blockade in the mNTS. Only atropine methylbromide
    altered baseline motility and prevented the effects of GABA(A) receptor
    blockade on gastric motility. Our data demonstrate the presence of
    intra-NTS GABAergic signaling between the vagal afferent nerve terminals
    and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic
    excitatory pathway comprises the functionally relevant efferent arm
    of the vagovagal circuit.
    BibTeX:
    @article{Herman2009,
      author = {Melissa A Herman and Maureen T Cruz and Niaz Sahibzada and Joseph Verbalis and Richard A Gillis},
      title = {GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit.},
      journal = {Am J Physiol Gastrointest Liver Physiol},
      school = {Interdisciplinary Program in Neuroscience, Georgetown Univ. Medical Center, 3900 Reservoir Rd., NW, Washington, DC 20057, USA.},
      year = {2009},
      volume = {296},
      number = {1},
      pages = {G101--G111},
      url = {http://dx.doi.org/10.1152/ajpgi.90504.2008},
      doi = {http://doi.org/10.1152/ajpgi.90504.2008}
    }
    
    Hoe, H.-S., Fu, Z., Makarova, A., Lee, J.-Y., Lu, C., Feng, L., Pajoohesh-Ganji, A., Matsuoka, Y., Hyman, B.T., Ehlers, M.D., Vicini, S., Pak, D.T.S. & Rebeck, G.W. The effects of amyloid precursor protein on postsynaptic composition and activity. 2009 J Biol Chem
    Vol. 284(13), pp. 8495-8506School: D. C. 20057-1464, USA. 
    DOI URL 
    Abstract: The amyloid precursor protein (APP) is cleaved to produce the Alzheimer
    disease-associated peptide Abeta, but the normal functions of uncleaved
    APP in the brain are unknown. We found that APP was present in the
    postsynaptic density of central excitatory synapses and coimmunoprecipitated
    with N-methyl-d-aspartate receptors (NMDARs). The presence of APP
    in the postsynaptic density was supported by the observation that
    NMDARs regulated trafficking and processing of APP; overexpression
    of the NR1 subunit increased surface levels of APP, whereas activation
    of NMDARs decreased surface APP and promoted production of Abeta.
    We transfected APP or APP RNA interference into primary neurons and
    used electrophysiological techniques to explore the effects of APP
    on postsynaptic function. Reduction of APP decreased (and overexpression
    of APP increased) NMDAR whole cell current density and peak amplitude
    of spontaneous miniature excitatory postsynaptic currents. The increase
    in NMDAR current by APP was due to specific recruitment of additional
    NR2B-containing receptors. Consistent with these findings, immunohistochemical
    experiments demonstrated that APP increased the surface levels and
    decreased internalization of NR2B subunits. These results demonstrate
    a novel physiological role of postsynaptic APP in enhancing NMDAR
    function.
    BibTeX:
    @article{Hoe2009b,
      author = {Hyang-Sook Hoe and Zhanyan Fu and Alexandra Makarova and Ji-Yun Lee and Congyi Lu and Li Feng and Ahdeah Pajoohesh-Ganji and Yasuji Matsuoka and Bradley T Hyman and Michael D Ehlers and Stefano Vicini and Daniel T S Pak and G. William Rebeck},
      title = {The effects of amyloid precursor protein on postsynaptic composition and activity.},
      journal = {J Biol Chem},
      school = { D. C. 20057-1464, USA.},
      year = {2009},
      volume = {284},
      number = {13},
      pages = {8495--8506},
      url = {http://dx.doi.org/10.1074/jbc.M900141200},
      doi = {http://doi.org/10.1074/jbc.M900141200}
    }
    
    Hoe, H.-S., Lee, J.-Y. & Pak, D.T.S. Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2. 2009 Biochem Biophys Res Commun
    Vol. 384(1), pp. 55-60School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Rap small GTPases regulate excitatory synaptic strength and morphological
    plasticity of dendritic spines. Changes in spine structure are mediated
    by the F-actin cytoskeleton, but the link between Rap activity and
    actin dynamics is unclear. Here, we report a novel interaction between
    SPAR, a postsynaptic inhibitor of Rap, and alpha-actinin, a family
    of actin-cross-linking proteins. SPAR and alpha-actinin engage in
    bidirectional structural plasticity of dendritic spines: SPAR promotes
    spine head enlargement, whereas increased alpha-actinin2 expression
    favors dendritic spine elongation and thinning. Surprisingly, SPAR
    and alpha-actinin2 can function in an additive rather than antagonistic
    fashion at the same dendritic spine, generating combination spine/filopodia
    hybrids. These data identify a molecular pathway bridging the actin
    cytoskeleton and Rap at synapses, and suggest that formation of spines
    and filopodia are not necessarily opposing forms of structural plasticity.
    BibTeX:
    @article{Hoe2009a,
      author = {Hyang-Sook Hoe and Ji-Yun Lee and Daniel T S Pak},
      title = {Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2.},
      journal = {Biochem Biophys Res Commun},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA.},
      year = {2009},
      volume = {384},
      number = {1},
      pages = {55--60},
      url = {http://dx.doi.org/10.1016/j.bbrc.2009.04.069},
      doi = {http://doi.org/10.1016/j.bbrc.2009.04.069}
    }
    
    Hoe, H.-S., Lee, K.J., Carney, R.S.E., Lee, J., Markova, A., Lee, J.-Y., Howell, B.W., Hyman, B.T., Pak, D.T.S., Bu, G. & Rebeck, G.W. Interaction of reelin with amyloid precursor protein promotes neurite outgrowth. 2009 J Neurosci
    Vol. 29(23), pp. 7459-7473School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: The processing of amyloid precursor protein (APP) to Abeta is an important
    event in the pathogenesis of Alzheimer's disease, but the physiological
    function of APP is not well understood. Our previous work has shown
    that APP processing and Abeta production are regulated by the extracellular
    matrix protein Reelin. In the present study, we examined whether
    Reelin interacts with APP, and the functional consequences of that
    interaction in vitro. Using coimmunoprecipitation, we found that
    Reelin interacted with APP through the central domain of Reelin (repeats
    3-6) and the E1 extracellular domain of APP. Reelin increased cell
    surface levels of APP and decreased endocytosis of APP in hippocampal
    neurons in vitro. In vivo, Reelin levels were increased in brains
    of APP knock-out mice and decreased in APP-overexpressing mice. RNA
    interference knockdown of APP decreased neurite outgrowth in vitro
    and prevented Reelin from increasing neurite outgrowth. Knock-out
    of APP or Reelin decreased dendritic arborization in cortical neurons
    in vivo, and APP overexpression increased dendritic arborization.
    APP and Reelin have previously been shown to promote neurite outgrowth
    through interactions with integrins. We confirmed that APP interacted
    with alpha3beta1 integrin, and alpha3beta1 integrin altered APP trafficking
    and processing. Addition of an alpha3beta1 integrin antibody prevented
    APP and Reelin-induced neurite outgrowth. These findings demonstrate
    that Reelin interacts with APP, potentially having important effects
    on neurite development.
    BibTeX:
    @article{Hoe2009,
      author = {Hyang-Sook Hoe and Kea Joo Lee and Rosalind S E Carney and Jiyeon Lee and Alexandra Markova and Ji-Yun Lee and Brian W Howell and Bradley T Hyman and Daniel T S Pak and Guojun Bu and G. William Rebeck},
      title = {Interaction of reelin with amyloid precursor protein promotes neurite outgrowth.},
      journal = {J Neurosci},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057-1464, USA.},
      year = {2009},
      volume = {29},
      number = {23},
      pages = {7459--7473},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.4872-08.2009},
      doi = {http://doi.org/10.1523/JNEUROSCI.4872-08.2009}
    }
    
    Leaver, A.M., Lare, J.V., Zielinski, B., Halpern, A.R. & Rauschecker, J.P. Brain activation during anticipation of sound sequences. 2009 J Neurosci
    Vol. 29(8), pp. 2477-2485School: Laboratory of Integrative Neuroscience and Cognition, Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Music consists of sound sequences that require integration over time.
    As we become familiar with music, associations between notes, melodies,
    and entire symphonic movements become stronger and more complex.
    These associations can become so tight that, for example, hearing
    the end of one album track can elicit a robust image of the upcoming
    track while anticipating it in total silence. Here, we study this
    predictive "anticipatory imagery" at various stages throughout learning
    and investigate activity changes in corresponding neural structures
    using functional magnetic resonance imaging. Anticipatory imagery
    (in silence) for highly familiar naturalistic music was accompanied
    by pronounced activity in rostral prefrontal cortex (PFC) and premotor
    areas. Examining changes in the neural bases of anticipatory imagery
    during two stages of learning conditional associations between simple
    melodies, however, demonstrates the importance of fronto-striatal
    connections, consistent with a role of the basal ganglia in "training"
    frontal cortex (Pasupathy and Miller, 2005). Another striking change
    in neural resources during learning was a shift between caudal PFC
    earlier to rostral PFC later in learning. Our findings regarding
    musical anticipation and sound sequence learning are highly compatible
    with studies of motor sequence learning, suggesting common predictive
    mechanisms in both domains.
    BibTeX:
    @article{Leaver2009,
      author = {Amber M Leaver and Jennifer Van Lare and Brandon Zielinski and Andrea R Halpern and Josef P Rauschecker},
      title = {Brain activation during anticipation of sound sequences.},
      journal = {J Neurosci},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2009},
      volume = {29},
      number = {8},
      pages = {2477--2485},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.4921-08.2009},
      doi = {http://doi.org/10.1523/JNEUROSCI.4921-08.2009}
    }
    
    Leaver, A.M., Van Lare, J., Zielinski, B., Halpern, A.R. & Rauschecker, J.P. Brain activation during anticipation of sound sequences. 2009 J Neurosci
    Vol. 29(8), pp. 2477-2485School: Laboratory of Integrative Neuroscience and Cognition, Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Music consists of sound sequences that require integration over time. As we become familiar with music, associations between notes, melodies, and entire symphonic movements become stronger and more complex. These associations can become so tight that, for example, hearing the end of one album track can elicit a robust image of the upcoming track while anticipating it in total silence. Here, we study this predictive "anticipatory imagery" at various stages throughout learning and investigate activity changes in corresponding neural structures using functional magnetic resonance imaging. Anticipatory imagery (in silence) for highly familiar naturalistic music was accompanied by pronounced activity in rostral prefrontal cortex (PFC) and premotor areas. Examining changes in the neural bases of anticipatory imagery during two stages of learning conditional associations between simple melodies, however, demonstrates the importance of fronto-striatal connections, consistent with a role of the basal ganglia in "training" frontal cortex (Pasupathy and Miller, 2005). Another striking change in neural resources during learning was a shift between caudal PFC earlier to rostral PFC later in learning. Our findings regarding musical anticipation and sound sequence learning are highly compatible with studies of motor sequence learning, suggesting common predictive mechanisms in both domains.
    BibTeX:
    @article{LeaverVanLareZielinskiEtAl2009,
      author = {Leaver, Amber M. and Van Lare, Jennifer and Zielinski, Brandon and Halpern, Andrea R. and Rauschecker, Josef P.},
      title = {Brain activation during anticipation of sound sequences.},
      journal = {J Neurosci},
      school = {Laboratory of Integrative Neuroscience and Cognition, Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA.},
      year = {2009},
      volume = {29},
      number = {8},
      pages = {2477--2485},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.4921-08.2009},
      doi = {http://doi.org/10.1523/JNEUROSCI.4921-08.2009}
    }
    
    Loane, D.J., Pocivavsek, A., Moussa, C.E.-H., Thompson, R., Matsuoka, Y., Faden, A.I., Rebeck, G.W. & Burns, M.P. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. 2009 Nat Med
    Vol. 15(4), pp. 377-379School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. 
    DOI URL 
    Abstract: Amyloid-beta (Abeta) peptides, found in Alzheimer's disease brain,
    accumulate rapidly after traumatic brain injury (TBI) in both humans
    and animals. Here we show that blocking either beta- or gamma-secretase,
    enzymes required for production of Abeta from amyloid precursor protein
    (APP), can ameliorate motor and cognitive deficits and reduce cell
    loss after experimental TBI in mice. Thus, APP secretases are promising
    targets for treatment of TBI.
    BibTeX:
    @article{Loane2009a,
      author = {David J Loane and Ana Pocivavsek and Charbel E-H Moussa and Rachel Thompson and Yasuji Matsuoka and Alan I Faden and G. William Rebeck and Mark P Burns},
      title = {Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury.},
      journal = {Nat Med},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.},
      year = {2009},
      volume = {15},
      number = {4},
      pages = {377--379},
      url = {http://dx.doi.org/10.1038/nm.1940},
      doi = {http://doi.org/10.1038/nm.1940}
    }
    
    Loane, D.J., Stoica, B.A., Pajoohesh-Ganji, A., Byrnes, K.R. & Faden, A.I. Activation of metabotropic glutamate receptor 5 modulates microglial reactivity and neurotoxicity by inhibiting NADPH oxidase. 2009 J Biol Chem
    Vol. 284(23), pp. 15629-15639School: Department of Neuroscience, Georgetown University Medical Center, Washington, D C 20057, USA. djl42@georgetown.edu 
    DOI URL 
    Abstract: Microglial-related factors have been implicated in the signaling cascades
    that contribute to neuronal cell death in various neurodegenerative
    disorders. Thus, strategies that reduce microglial activation and
    associated neurotoxicity may have therapeutic benefit. Group II and
    III metabotropic glutamate receptors (mGluRs) are expressed in microglia
    and can modulate microglial activity in primary cell cultures. We
    demonstrate that the group I receptor member mGluR5 is highly expressed
    in primary microglial cultures and the BV2 microglial cell line.
    Activation of mGluR5 using the selective agonist (RS)-2-chloro-5-hydroxyphenylglycine
    (CHPG) significantly attenuates microglial activation in response
    to lipopolysaccharide and interferon-gamma, as indicated by a reduction
    in the expression of inducible nitric-oxide synthase, production
    of nitric oxide and tumor necrosis factor-alpha, and intracellular
    generation of reactive oxygen species. In addition, microglial-induced
    neurotoxicity is also markedly reduced by CHPG treatment. The anti-inflammatory
    effects of CHPG are mediated by the mGluR5 receptor, because either
    a selective mGluR5 antagonist or small interference RNA knockdown
    attenuated the actions of this drug. CHPG blocked the lipopolysaccharide-induced
    increase in expression and enzymatic activity of NADPH oxidase. Moreover,
    the protective effects of CHPG were significantly reduced when the
    NADPH oxidase subunits p22(phox) or gp91(phox) were knocked down
    by small interference RNA. These data suggest that mGluR5 represents
    a novel target for modulating microglial-dependent neuroinflammation,
    and may have therapeutic relevance for neurological disorders that
    exhibit microglial-mediated neurodegeneration.
    BibTeX:
    @article{Loane2009,
      author = {David J Loane and Bogdan A Stoica and Ahdeah Pajoohesh-Ganji and Kimberly R Byrnes and Alan I Faden},
      title = {Activation of metabotropic glutamate receptor 5 modulates microglial reactivity and neurotoxicity by inhibiting NADPH oxidase.},
      journal = {J Biol Chem},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, D C 20057, USA. djl42@georgetown.edu},
      year = {2009},
      volume = {284},
      number = {23},
      pages = {15629--15639},
      url = {http://dx.doi.org/10.1074/jbc.M806139200},
      doi = {http://doi.org/10.1074/jbc.M806139200}
    }
    
    Lytle, J.M., Chittajallu, R., Wrathall, J.R. & Gallo, V. NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury. 2009 Glia
    Vol. 57(3), pp. 270-285School: Department of Neuroscience, Georgetown University, Washington, District of Columbia, USA. 
    DOI URL 
    Abstract: NG2(+) cells in the adult CNS are a heterogeneous population. The
    extent to which the subpopulation of NG2(+) cells that function as
    oligodendrocyte progenitor cells (OPCs) respond to spinal cord injury
    (SCI) and recapitulate their normal developmental progression remains
    unclear. We used the CNP-EGFP mouse, in which oligodendrocyte lineage
    cells express EGFP, to study NG2(+) cells in the normal and injured
    spinal cord. In white matter of uninjured mice, bipolar EGFP(+)NG2(+)
    cells and multipolar EGFP(neg)NG2(+) cells were identified. After
    SCI, EGFP(+)NG2(+) cell proliferation in residual white matter peaked
    at 3 days post injury (DPI) rostral to the epicenter, while EGFP(neg)NG2(+)
    cell proliferation peaked at 7 DPI at the epicenter. The expression
    of transcription factors, Olig2, Sox10, and Sox17, and the basic
    electrophysiological membrane parameters and potassium current phenotype
    of the EGFP(+)NG2(+) population after injury were consistent with
    those of proliferative OPCs during development. EGFP(neg)NG2(+) cells
    did not express transcription factors involved in oligodendrogenesis.
    EGFP(+)CC1(+) oligodendrocytes at 6 weeks included cells that incorporated
    BrdU during the peak of EGFP(+)NG2(+) cell proliferation. EGFP(neg)CC1(+)
    oligodendrocytes were never observed. Treatment with glial growth
    factor 2 and fibroblast growth factor 2 enhanced oligodendrogenesis
    and increased the number of EGFP(neg)NG2(+) cells. Therefore, based
    on EGFP and transcription factor expression, spatiotemporal proliferation
    patterns, and response to growth factors, two populations of NG2(+)
    cells can be identified that react to SCI. The EGFP(+)NG2(+) cells
    undergo cellular and physiological changes in response to SCI that
    are similar to those that occur in early postnatal NG2(+) cells during
    developmental oligodendrogenesis.
    BibTeX:
    @article{Lytle2009,
      author = {Judith M Lytle and Ramesh Chittajallu and Jean R Wrathall and Vittorio Gallo},
      title = {NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury.},
      journal = {Glia},
      school = {Department of Neuroscience, Georgetown University, Washington, District of Columbia, USA.},
      year = {2009},
      volume = {57},
      number = {3},
      pages = {270--285},
      url = {http://dx.doi.org/10.1002/glia.20755},
      doi = {http://doi.org/10.1002/glia.20755}
    }
    
    Maguire-Zeiss, K.A. & Federoff, H.J. Immune-directed gene therapeutic development for Alzheimer's, prion, and Parkinson's diseases. 2009 J Neuroimmune Pharmacol
    Vol. 4(3), pp. 298-308School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. km445@georgetown.edu 
    DOI URL 
    Abstract: The development of novel immune-based therapeutics for neurodegenerative
    diseases is an area of intense focus. Neurodegenerative diseases
    represent a particular challenge since in many cases the onset of
    symptoms occurs after considerable degeneration has ensued. Based
    on human genetic and histopathological evidence from patients with
    neurodegenerative diseases, animal models that recapitulate specific
    pathologic features have been developed. Utilizing these animal models
    in combination with viral vector-based gene therapeutics, specific
    epochs of disease can be targeted. One common feature of several
    neurodegenerative diseases is misfolded proteins. The mechanism by
    which these altered protein conformers lead to neurodegeneration
    is not completely understood but much effort has been put forward
    to either degrade aberrant protein or prevent the formation of misfolded
    conformers. In this review, we will summarize work that employs viral
    vector gene therapeutics to modulate the brain's response to misfolded
    proteins with a specific focus on neurodegeneration.
    BibTeX:
    @article{Maguire-Zeiss2009,
      author = {Kathleen A Maguire-Zeiss and Howard J Federoff},
      title = {Immune-directed gene therapeutic development for Alzheimer's, prion, and Parkinson's diseases.},
      journal = {J Neuroimmune Pharmacol},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. km445@georgetown.edu},
      year = {2009},
      volume = {4},
      number = {3},
      pages = {298--308},
      url = {http://dx.doi.org/10.1007/s11481-008-9133-3},
      doi = {http://doi.org/10.1007/s11481-008-9133-3}
    }
    
    Mocchetti, I. The areas of pathology, biomolecular mechanisms, and therapeutic approaches. Preface. 2009 Neurotox Res
    Vol. 16(3), pp. 185School: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. moccheti@georgetown.edu 
    DOI URL 
    BibTeX:
    @article{Mocchetti2009,
      author = {Italo Mocchetti},
      title = {The areas of pathology, biomolecular mechanisms, and therapeutic approaches. Preface.},
      journal = {Neurotox Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. moccheti@georgetown.edu},
      year = {2009},
      volume = {16},
      number = {3},
      pages = {185},
      url = {http://dx.doi.org/10.1007/s12640-009-9089-y},
      doi = {http://doi.org/10.1007/s12640-009-9089-y}
    }
    
    Palchik, G. Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009. 2009 Philos Ethics Humanit Med
    Vol. 4, pp. 9School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu 
    DOI URL 
    Abstract: This reviews the first of a tripartite symposia series dealing with
    novel neuroscientific technologies, the nature of consciousness and
    being, and the questions that arise from such interactions. The event
    took place on May 8 2009, at Georgetown University, and brought together
    ten leading figures on fields ranging from Neuroscience and Robotics
    to Philosophy, that commented on their research and provided ethical,
    moral and practical insight and perspectives into how these technologies
    can shape the future of neuroscientific and human development, as
    well as denoting the potential abuses and the best way to proceed
    about them.
    BibTeX:
    @article{Palchik2009,
      author = {Guillermo Palchik},
      title = {Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009.},
      journal = {Philos Ethics Humanit Med},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu},
      year = {2009},
      volume = {4},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1747-5341-4-9},
      doi = {http://doi.org/10.1186/1747-5341-4-9}
    }
    
    Palchik, G. Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009. 2009 Philos Ethics Humanit Med
    Vol. 4, pp. 9School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu 
    DOI URL 
    Abstract: This reviews the first of a tripartite symposia series dealing with
    novel neuroscientific technologies, the nature of consciousness and
    being, and the questions that arise from such interactions. The event
    took place on May 8 2009, at Georgetown University, and brought together
    ten leading figures on fields ranging from Neuroscience and Robotics
    to Philosophy, that commented on their research and provided ethical,
    moral and practical insight and perspectives into how these technologies
    can shape the future of neuroscientific and human development, as
    well as denoting the potential abuses and the best way to proceed
    about them.
    BibTeX:
    @article{Palchik2009a,
      author = {Palchik, Guillermo},
      title = {Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009.},
      journal = {Philos Ethics Humanit Med},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu},
      year = {2009},
      volume = {4},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1747-5341-4-9},
      doi = {http://doi.org/10.1186/1747-5341-4-9}
    }
    
    Palchik, G. Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009. 2009 Philos Ethics Humanit Med
    Vol. 4, pp. 9School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu 
    DOI URL 
    Abstract: This reviews the first of a tripartite symposia series dealing with
    novel neuroscientific technologies, the nature of consciousness and
    being, and the questions that arise from such interactions. The event
    took place on May 8 2009, at Georgetown University, and brought together
    ten leading figures on fields ranging from Neuroscience and Robotics
    to Philosophy, that commented on their research and provided ethical,
    moral and practical insight and perspectives into how these technologies
    can shape the future of neuroscientific and human development, as
    well as denoting the potential abuses and the best way to proceed
    about them.
    BibTeX:
    @article{Palchik2009b,
      author = {Palchik, Guillermo},
      title = {Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009.},
      journal = {Philos Ethics Humanit Med},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu},
      year = {2009},
      volume = {4},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1747-5341-4-9},
      doi = {http://doi.org/10.1186/1747-5341-4-9}
    }
    
    Palchik, G. Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009. 2009 Philos Ethics Humanit Med
    Vol. 4, pp. 9School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu 
    DOI URL 
    Abstract: This reviews the first of a tripartite symposia series dealing with
    novel neuroscientific technologies, the nature of consciousness and
    being, and the questions that arise from such interactions. The event
    took place on May 8 2009, at Georgetown University, and brought together
    ten leading figures on fields ranging from Neuroscience and Robotics
    to Philosophy, that commented on their research and provided ethical,
    moral and practical insight and perspectives into how these technologies
    can shape the future of neuroscientific and human development, as
    well as denoting the potential abuses and the best way to proceed
    about them.
    BibTeX:
    @article{Palchik2009c,
      author = {Palchik, Guillermo},
      title = {Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009.},
      journal = {Philos Ethics Humanit Med},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu},
      year = {2009},
      volume = {4},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1747-5341-4-9},
      doi = {http://doi.org/10.1186/1747-5341-4-9}
    }
    
    Palchik, G. Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009. 2009 Philos Ethics Humanit Med
    Vol. 4, pp. 9School: Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu 
    DOI URL 
    Abstract: This reviews the first of a tripartite symposia series dealing with
    novel neuroscientific technologies, the nature of consciousness and
    being, and the questions that arise from such interactions. The event
    took place on May 8 2009, at Georgetown University, and brought together
    ten leading figures on fields ranging from Neuroscience and Robotics
    to Philosophy, that commented on their research and provided ethical,
    moral and practical insight and perspectives into how these technologies
    can shape the future of neuroscientific and human development, as
    well as denoting the potential abuses and the best way to proceed
    about them.
    BibTeX:
    @article{Palchik2009d,
      author = {Palchik, Guillermo},
      title = {Conference report: the Nour Foundation Georgetown University & Blackfriars Hall,Oxford University Symposium Series Technology, Neuroscience & the Nature of Being: Considerations of Meaning, Morality and Transcendence part I: The Paradox of Neurotechnology 8 May 2009.},
      journal = {Philos Ethics Humanit Med},
      school = {Interdisciplinary Program in Neuroscience, Georgetown University Medical Center Washington, DC, USA. gp62@georgetown.edu},
      year = {2009},
      volume = {4},
      pages = {9},
      url = {http://dx.doi.org/10.1186/1747-5341-4-9},
      doi = {http://doi.org/10.1186/1747-5341-4-9}
    }
    
    Pocivavsek, A., Burns, M.P. & Rebeck, G.W. Low-density lipoprotein receptors regulate microglial inflammation through c-Jun N-terminal kinase. 2009 Glia
    Vol. 57(4), pp. 444-453School: Department of Neuroscience, Georgetown University, New Research Building, Washington, District of Columbia 20057-1464, USA. 
    DOI URL 
    Abstract: Apolipoprotein E (apoE) has been implicated in modulating the central
    nervous system (CNS) inflammatory response. However, the molecular
    mechanisms involved in apoE-dependent immunomodulation are poorly
    understood. We hypothesize that apoE alters the CNS inflammatory
    response by signaling via low-density lipoprotein (LDL) receptors
    in glia. To address this hypothesis, we used a small bioactive peptide
    formed from the receptor-binding domain of apoE, apoE peptide (EP),
    to study LDL receptor signaling in microglia. To model glial activation,
    we treated primary mouse microglia and the microglial cell line BV2
    with lipopolysaccharide (LPS) and studied two inflammatory responses:
    an increase in nitric oxide production (NO) and a decrease in apoE
    production. We found that treatment of primary microglia and BV2
    cells with EP attenuated LPS-induced NO accumulation and apoE reduction
    in a dose-dependent manner. Using the receptor-associated protein
    to block ligand binding to members of the LDL receptor family, we
    found that EP attenuated both of these LPS-induced inflammatory responses
    via LDL receptors. We studied two intracellular signaling cascades
    associated with apoE: c-Jun N-terminal kinase (JNK) and extracellular
    signal-regulated kinase (ERK). LPS induced both ERK and JNK activation,
    whereas EP induced ERK activation, but drastically reduced JNK activation.
    Inhibition of JNK with SP600125 reduced LPS-induced NO production
    and apoE reduction in a dose-dependent manner. Treatment of microglia
    with suboptimal EP in combination with JNK inhibitor enhanced attenuation
    of LPS-induced NO production. These data suggest that microglial
    LDL receptors regulate JNK activation, which is necessary for apoE
    modulation of the inflammatory response.
    BibTeX:
    @article{Pocivavsek2009b,
      author = {Ana Pocivavsek and Mark P Burns and G. William Rebeck},
      title = {Low-density lipoprotein receptors regulate microglial inflammation through c-Jun N-terminal kinase.},
      journal = {Glia},
      school = {Department of Neuroscience, Georgetown University, New Research Building, Washington, District of Columbia 20057-1464, USA.},
      year = {2009},
      volume = {57},
      number = {4},
      pages = {444--453},
      url = {http://dx.doi.org/10.1002/glia.20772},
      doi = {http://doi.org/10.1002/glia.20772}
    }
    
    Pocivavsek, A., Mikhailenko, I., Strickland, D.K. & Rebeck, G.W. Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation. 2009 J Neuroimmunol
    Vol. 214(1-2), pp. 25-32School: Department of Neuroscience, Georgetown University, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Apolipoprotein E (apoE)-induced activation of low-density lipoprotein
    receptor (LDL) family members reduces inflammatory responses by suppressing
    c-Jun N-terminal kinase (JNK) activation. We aimed to identify which
    specific receptor family member mediates the effect of apoE on inflammation
    in primary cultures of microglia. Low-density lipoprotein receptor-related
    protein 1 (LRP1)-deficient (LRP1-/-) microglia were derived from
    mice using tissue-specific loxP/Cre recombination. Using a peptide
    formed from the receptor-binding region of apoE (EP), we found that
    LRP1 mediates the effects of apoE on microglial inflammation. Microglial
    LRP1 was also essential for EP to suppress JNK activation induced
    by lipopolysaccharide.
    BibTeX:
    @article{Pocivavsek2009a,
      author = {Ana Pocivavsek and Irina Mikhailenko and Dudley K Strickland and G. William Rebeck},
      title = {Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation.},
      journal = {J Neuroimmunol},
      school = {Department of Neuroscience, Georgetown University, Washington, DC 20057-1464, USA.},
      year = {2009},
      volume = {214},
      number = {1-2},
      pages = {25--32},
      url = {http://dx.doi.org/10.1016/j.jneuroim.2009.06.010},
      doi = {http://doi.org/10.1016/j.jneuroim.2009.06.010}
    }
    
    Pocivavsek, A. & Rebeck, G.W. Inhibition of c-Jun N-terminal kinase increases apoE expression in vitro and in vivo. 2009 Biochem Biophys Res Commun
    Vol. 387(3), pp. 516-520School: Department of Neuroscience, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA. 
    DOI URL 
    Abstract: Apolipoprotein E (apoE), a ligand for the low-density lipoprotein
    receptor family, has been implicated in modulating glial inflammatory
    responses and the risk of neurodegeneration associated with Alzheimer's
    disease. Glial cells activated by lipopolysaccharide (LPS) have decreased
    apoE levels and we recently showed that apoE itself can modulate
    the inflammatory response by reducing c-Jun N-terminal kinase (JNK)
    activation. Reduced JNK phosphorylation is vital to overcome the
    LPS-induced decrease in apoE expression, suggesting that JNK inhibition
    may be an effective way to increase apoE protein and protract its
    anti-inflammatory properties. This study investigates the impact
    of JNK inhibition on apoE production using two JNK inhibitors. Our
    work in primary glia and in vivo in mice injected with JNK inhibitor
    demonstrates that inhibition of JNK may be an effective way to increase
    apoE expression.
    BibTeX:
    @article{Pocivavsek2009,
      author = {Ana Pocivavsek and G. William Rebeck},
      title = {Inhibition of c-Jun N-terminal kinase increases apoE expression in vitro and in vivo.},
      journal = {Biochem Biophys Res Commun},
      school = {Department of Neuroscience, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA.},
      year = {2009},
      volume = {387},
      number = {3},
      pages = {516--520},
      url = {http://dx.doi.org/10.1016/j.bbrc.2009.07.048},
      doi = {http://doi.org/10.1016/j.bbrc.2009.07.048}
    }
    
    Prado, E.L. & Ullman, M.T. Can imageability help us draw the line between storage and composition? 2009 J Exp Psychol Learn Mem Cogn
    Vol. 35(4), pp. 849-866School: Department of Neuroscience, Georgetown University, Washington, DC, USA. 
    DOI URL 
    Abstract: Language requires both storage and composition. However, exactly what
    is retrieved from memory and what is assembled remains controversial,
    especially for inflected words. Here, "imageability effects" is introduced
    as a new diagnostic of storage and a complement to frequency effects.
    In 2 studies of past-tense morphology, more reliable imageability
    and frequency effects were found on irregulars than on regulars.
    An interaction with sex was also observed: Males but not females
    showed more reliable frequency and imageability effects for irregulars
    than for regulars; females but not males showed signs of storage
    for regulars, particularly among higher frequency forms. Overall,
    the findings validate imageability effects as another diagnostic
    of storage and suggest that the line between storage and computation
    is not a simple function; rather, it depends upon the interplay of
    both item- and subject-specific factors.
    BibTeX:
    @article{Prado2009,
      author = {Elizabeth L Prado and Michael T Ullman},
      title = {Can imageability help us draw the line between storage and composition?},
      journal = {J Exp Psychol Learn Mem Cogn},
      school = {Department of Neuroscience, Georgetown University, Washington, DC, USA.},
      year = {2009},
      volume = {35},
      number = {4},
      pages = {849--866},
      url = {http://dx.doi.org/10.1037/a0015286},
      doi = {http://doi.org/10.1037/a0015286}
    }
    
    Rauschecker, J.P. & Scott, S.K. Maps and streams in the auditory cortex: nonhuman primates illuminate human speech processing. 2009 Nat Neurosci
    Vol. 12(6), pp. 718-724School: Laboratory of Integrative Neuroscience and Cognition, Georgetown University Medical Center, Washington, DC, USA. rauschej@georgetown.edu 
    DOI URL 
    Abstract: Speech and language are considered uniquely human abilities: animals
    have communication systems, but they do not match human linguistic
    skills in terms of recursive structure and combinatorial power. Yet,
    in evolution, spoken language must have emerged from neural mechanisms
    at least partially available in animals. In this paper, we will demonstrate
    how our understanding of speech perception, one important facet of
    language, has profited from findings and theory in nonhuman primate
    studies. Chief among these are physiological and anatomical studies
    showing that primate auditory cortex, across species, shows patterns
    of hierarchical structure, topographic mapping and streams of functional
    processing. We will identify roles for different cortical areas in
    the perceptual processing of speech and review functional imaging
    work in humans that bears on our understanding of how the brain decodes
    and monitors speech. A new model connects structures in the temporal,
    frontal and parietal lobes linking speech perception and production.
    BibTeX:
    @article{Rauschecker2009,
      author = {Josef P Rauschecker and Sophie K Scott},
      title = {Maps and streams in the auditory cortex: nonhuman primates illuminate human speech processing.},
      journal = {Nat Neurosci},
      school = {Laboratory of Integrative Neuroscience and Cognition, Georgetown University Medical Center, Washington, DC, USA. rauschej@georgetown.edu},
      year = {2009},
      volume = {12},
      number = {6},
      pages = {718--724},
      url = {http://dx.doi.org/10.1038/nn.2331},
      doi = {http://doi.org/10.1038/nn.2331}
    }
    
    Rebeck, G.W. Nontraditional signaling mechanisms of lipoprotein receptors. 2009 Sci Signal
    Vol. 2(68), pp. pe28School: Department of Neuroscience, Georgetown University, Washington, DC 20007, USA. gwr2@georgetown.edu 
    DOI URL 
    Abstract: The low-density lipoprotein receptor family consists of a large number
    of single transmembrane proteins that are involved both in endocytosis
    of extracellular ligands and in intracellular signaling processes.
    New evidence ties these receptors to the transactivation of Trk receptors.
    Thus, this single receptor family demonstrates several distinct mechanisms
    for transducing information across the plasma membrane.
    BibTeX:
    @article{Rebeck2009,
      author = {G. William Rebeck},
      title = {Nontraditional signaling mechanisms of lipoprotein receptors.},
      journal = {Sci Signal},
      school = {Department of Neuroscience, Georgetown University, Washington, DC 20007, USA. gwr2@georgetown.edu},
      year = {2009},
      volume = {2},
      number = {68},
      pages = {pe28},
      url = {http://dx.doi.org/10.1126/scisignal.268pe28},
      doi = {http://doi.org/10.1126/scisignal.268pe28}
    }
    
    Renier, L.A., Anurova, I., Volder, A.G.D., Carlson, S., VanMeter, J. & Rauschecker, J.P. Multisensory integration of sounds and vibrotactile stimuli in processing streams for "what" and "where". 2009 J Neurosci
    Vol. 29(35), pp. 10950-10960School: Department of Physiology and Biophysics, Laboratory for Integrative Neuroscience and Cognition, Georgetown University Medical Center, Washington, DC 20007, USA. 
    DOI URL 
    Abstract: The segregation between cortical pathways for the identification and
    localization of objects is thought of as a general organizational
    principle in the brain. Yet, little is known about the unimodal versus
    multimodal nature of these processing streams. The main purpose of
    the present study was to test whether the auditory and tactile dual
    pathways converged into specialized multisensory brain areas. We
    used functional magnetic resonance imaging (fMRI) to compare directly
    in the same subjects the brain activation related to localization
    and identification of comparable auditory and vibrotactile stimuli.
    Results indicate that the right inferior frontal gyrus (IFG) and
    both left and right insula were more activated during identification
    conditions than during localization in both touch and audition. The
    reverse dissociation was found for the left and right inferior parietal
    lobules (IPL), the left superior parietal lobule (SPL) and the right
    precuneus-SPL, which were all more activated during localization
    conditions in the two modalities. We propose that specialized areas
    in the right IFG and the left and right insula are multisensory operators
    for the processing of stimulus identity whereas parts of the left
    and right IPL and SPL are specialized for the processing of spatial
    attributes independently of sensory modality.
    BibTeX:
    @article{Renier2009,
      author = {Laurent A Renier and Irina Anurova and Anne G De Volder and Synn?ve Carlson and John VanMeter and Josef P Rauschecker},
      title = {Multisensory integration of sounds and vibrotactile stimuli in processing streams for "what" and "where".},
      journal = {J Neurosci},
      school = {Department of Physiology and Biophysics, Laboratory for Integrative Neuroscience and Cognition, Georgetown University Medical Center, Washington, DC 20007, USA.},
      year = {2009},
      volume = {29},
      number = {35},
      pages = {10950--10960},
      url = {http://dx.doi.org/10.1523/JNEUROSCI.0910-09.2009},
      doi = {http://doi.org/10.1523/JNEUROSCI.0910-09.2009}
    }
    
    Riesenhuber, M. & Wolff, B.S. Task effects, performance levels, features, configurations, and holistic face processing: a reply to Rossion. 2009 Acta Psychol (Amst)
    Vol. 132(3), pp. 286-292School: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA. mr287@georgetown.edu 
    DOI URL 
    Abstract: A recent article in Acta Psychologica ("Picture-plane inversion leads
    to qualitative changes of face perception" by Rossion [Rossion, B.
    (2008). Picture-plane inversion leads to qualitative changes of face
    perception. Acta Psychologica (Amst), 128(2), 274-289]) criticized
    several aspects of an earlier paper of ours [Riesenhuber, M., Jarudi,
    I., Gilad, S., & Sinha, P. (2004). Face processing in humans is compatible
    with a simple shape-based model of vision. Proceedings of the Royal
    Society of London B (Supplements), 271, S448-S450]. We here address
    Rossion's criticisms and correct some misunderstandings. To frame
    the discussion, we first review our previously presented computational
    model of face recognition in cortex [Jiang, X., Rosen, E., Zeffiro,
    T., Vanmeter, J., Blanz, V., & Riesenhuber, M. (2006). Evaluation
    of a shape-based model of human face discrimination using FMRI and
    behavioral techniques. Neuron, 50(1), 159-172] that provides a concrete
    biologically plausible computational substrate for holistic coding,
    namely a neural representation learned for upright faces, in the
    spirit of the original simple-to-complex hierarchical model of vision
    by Hubel and Wiesel. We show that Rossion's and others' data support
    the model, and that there is actually a convergence of views on the
    mechanisms underlying face recognition, in particular regarding holistic
    processing.
    BibTeX:
    @article{Riesenhuber2009,
      author = {Maximilian Riesenhuber and Brian S Wolff},
      title = {Task effects, performance levels, features, configurations, and holistic face processing: a reply to Rossion.},
      journal = {Acta Psychol (Amst)},
      school = {Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA. mr287@georgetown.edu},
      year = {2009},
      volume = {132},
      number = {3},
      pages = {286--292},
      url = {http://dx.doi.org/10.1016/j.actpsy.2009.07.004},
      doi = {http://doi.org/10.1016/j.actpsy.2009.07.004}
    }
    
    Shimoji, M., Pagan, F., Healton, E.B. & Mocchetti, I. CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinson's disease. 2009 Neurotox Res
    Vol. 16(3), pp. 318-328School: Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, 3970 Reservoir Rd, NW, Box 571464, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: Except for a handful of inherited cases related to known gene defects,
    Parkinson's disease (PD) is a sporadic neurodegenerative disease
    of unknown etiology. There is increasing evidence that inflammation
    and proliferation of microglia may contribute to the neuronal damage
    seen in the nigro-striatal dopaminergic system of PD patients. Microglia
    events that participate in neuronal injury include the release of
    pro-inflammatory and neurotoxic factors. Characterizing these factors
    may help to prevent the exacerbation of PD symptoms or to remediate
    the disease progression. In rodents, the nigro-striatal system exhibits
    high expression of the chemokine receptor CXCR4. Its natural ligand
    CXCL12 can promote neuronal apoptosis. Therefore, the present study
    investigated the expression of CXCR4 and CXCL12 in post-mortem brains
    of PD and control (non-PD) individuals and in an animal model of
    PD. In the human substantia nigra (SN), CXCR4 immunoreactivity was
    high in dopaminergic neurons. Interestingly, the SN of PD subjects
    exhibited higher expression of CXCR4 expression and CXCL12 than control
    subjects despite the loss of dopamine (DA) neurons. This effect was
    accompanied by an increase in activated microglia. However, results
    from post-mortem brains may not provide indication as to whether
    CXCL12/CXCR4 can cause the degeneration of DA neurons. To examine
    the role of these chemokines, we determined the levels of CXCL12
    and CXCR4 in the SN of MPTP-treated mice. MPTP produced a time-dependent
    up-regulation of CXCR4 that preceded the loss of DA neurons. These
    results suggest that CXCL12/CXCR4 may participate in the etiology
    of PD and indicate a new possible target molecule for PD.
    BibTeX:
    @article{Shimoji2009,
      author = {Mika Shimoji and Fernando Pagan and Edward B Healton and Italo Mocchetti},
      title = {CXCR4 and CXCL12 expression is increased in the nigro-striatal system of Parkinson's disease.},
      journal = {Neurotox Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Research Building, Room EP04, 3970 Reservoir Rd, NW, Box 571464, Washington, DC 20057, USA.},
      year = {2009},
      volume = {16},
      number = {3},
      pages = {318--328},
      url = {http://dx.doi.org/10.1007/s12640-009-9076-3},
      doi = {http://doi.org/10.1007/s12640-009-9076-3}
    }
    
    Song, S. Consciousness and the consolidation of motor learning. 2009 Behav Brain Res
    Vol. 196(2), pp. 180-186School: Interdisciplinary Program in Neuroscience, Department of Psychology, Georgetown University, Washington, DC 20057, USA. sss35@georgetown.edu 
    DOI URL 
    Abstract: It is no secret that motor learning benefits from repetition. For
    example, pianists devote countless hours to performing complicated
    sequences of key presses, and golfers practice their swings thousands
    of times to reach a level of proficiency. Interestingly, the subsequent
    waking and sleeping hours after practice also play important roles
    in motor learning. During this time, a motor skill can consolidate
    into a more stable form that can lead to improved future performance
    without intervening practice. Though it is widely believed that sleep
    is crucial for this consolidation of motor learning, this is not
    generally true. In many instances only day-time consolidates motor
    learning, while in other instances neither day-time nor sleep consolidates
    learning. Recent studies have suggested that conscious awareness
    during motor training can determine whether sleep or day-time plays
    a role in consolidation. However, ongoing studies suggest that this
    explanation is also incomplete. In addition to conscious awareness,
    attention is an important factor to consider. This review discusses
    how attention and conscious awareness interact with day and night
    processes to consolidate a motor memory.
    BibTeX:
    @article{Song2009,
      author = {Sunbin Song},
      title = {Consciousness and the consolidation of motor learning.},
      journal = {Behav Brain Res},
      school = {Interdisciplinary Program in Neuroscience, Department of Psychology, Georgetown University, Washington, DC 20057, USA. sss35@georgetown.edu},
      year = {2009},
      volume = {196},
      number = {2},
      pages = {180--186},
      url = {http://dx.doi.org/10.1016/j.bbr.2008.09.034},
      doi = {http://doi.org/10.1016/j.bbr.2008.09.034}
    }
    
    Stoica, B.A., Byrnes, K.R. & Faden, A.I. Cell cycle activation and CNS injury. 2009 Neurotox Res
    Vol. 16(3), pp. 221-237School: Department of Neuroscience, Georgetown University School of Medicine, Research Building, Room WG18, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. stoicab@georgetown.edu 
    DOI URL 
    Abstract: Although traditionally it was believed that adult neurons have entered
    a permanent post-mitotic phase, the latest experimental data indicate
    that cell cycle constituents critically affect normal functions of
    the adult central nervous system (CNS), as well as contribute to
    the pathophysiology of both acute and chronic neurodegenerative disorders.
    Recent study has also suggested that cell cycle pathways are involved
    in mediating not only neuronal cell death but also glial changes
    which may play key roles in the pathophysiological mechanisms underlying
    acute and chronic neurodegenerative disorders. Therefore, therapies
    that inhibit cell cycle may have robust neuroprotective profiles,
    particularly after acute insults, by targeting multiple pathogenic
    mechanisms and could be useful clinically if used with a delivery
    focused on specific areas and of a limited duration.
    BibTeX:
    @article{Stoica2009,
      author = {Bogdan A Stoica and Kimberly R Byrnes and Alan I Faden},
      title = {Cell cycle activation and CNS injury.},
      journal = {Neurotox Res},
      school = {Department of Neuroscience, Georgetown University School of Medicine, Research Building, Room WG18, 3970 Reservoir Rd, NW, Washington, DC 20057, USA. stoicab@georgetown.edu},
      year = {2009},
      volume = {16},
      number = {3},
      pages = {221--237},
      url = {http://dx.doi.org/10.1007/s12640-009-9050-0},
      doi = {http://doi.org/10.1007/s12640-009-9050-0}
    }
    
    Stoica, B., Byrnes, K. & Faden, A.I. Multifunctional drug treatment in neurotrauma. 2009 Neurotherapeutics
    Vol. 6(1), pp. 14-27School: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. stoicab@georgetown.edu 
    DOI URL 
    Abstract: Although the concepts of secondary injury and neuroprotection after
    neurotrauma are experimentally well supported, clinical trials of
    neuroprotective agents in traumatic brain injury or spinal cord injury
    have been disappointing. Most strategies to date have used drugs
    directed toward a single pathophysiological mechanism that contributes
    to early necrotic cell death. Given these failures, recent research
    has increasingly focused on multifunctional (i.e., multipotential,
    pluripotential) agents that target multiple injury mechanisms, particularly
    those that occur later after the insult. Here we review two such
    approaches that show particular promise in experimental neurotrauma:
    cell cycle inhibitors and small cyclized peptides. Both show extended
    therapeutic windows for treatment and appear to share at least one
    important target.
    BibTeX:
    @article{Stoica2009a,
      author = {Bogdan Stoica and Kimberly Byrnes and Alan I Faden},
      title = {Multifunctional drug treatment in neurotrauma.},
      journal = {Neurotherapeutics},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. stoicab@georgetown.edu},
      year = {2009},
      volume = {6},
      number = {1},
      pages = {14--27},
      url = {http://dx.doi.org/10.1016/j.nurt.2008.10.029},
      doi = {http://doi.org/10.1016/j.nurt.2008.10.029}
    }
    
    Walenski, M., Sosta, K., Cappa, S. & Ullman, M.T. Deficits on irregular verbal morphology in Italian-speaking Alzheimer's disease patients. 2009 Neuropsychologia
    Vol. 47(5), pp. 1245-1255School: Brain and Language Laboratory, Department of Neuroscience, Georgetown University, Washington, DC 20057-1464, United States. mwalenski@ucsd.edu 
    DOI URL 
    Abstract: Studies of English have shown that temporal-lobe patients, including
    those with Alzheimer's disease, are spared at processing real and
    novel regular inflected forms (e.g., walk-->walked; blick-->blicked),
    but impaired at real and novel irregular forms (e.g., dig-->dug;
    spling-->splang). Here we extend the investigation cross-linguistically
    to the more complex system of Italian verbal morphology, allowing
    us to probe the generality of the previous findings in English, as
    well as to test different explanatory accounts of inflectional morphology.
    We examined the production of real and novel regular and irregular
    past-participle and present-tense forms by native Italian-speaking
    healthy control subjects and patients with probable Alzheimer's disease.
    Compared to the controls, the patients were impaired at inflecting
    real irregular verbs but not real regular verbs both for past-participle
    and present-tense forms, but were not impaired at real regular verbs
    either for past-participle or present-tense forms. For novel past
    participles, the patients exhibited this same pattern of impaired
    production of class II (irregular) forms but spared class I (regular)
    production. In the present-tense, patients were impaired at the production
    of class II forms (which are regular in the present-tense), but spared
    at production of class I (regular) forms. Contrary to the pattern
    observed in English, the errors made by the patients on irregulars
    did not reveal a predominance of regularization errors (e.g., dig-->digged).
    The findings thus partly replicate prior findings from English, but
    also reveal new patterns from a language with a more complex morphological
    system that includes verb classes (which are not possible to test
    in English). The demonstration of an irregular deficit following
    temporal-lobe damage in a language other than English reveals the
    cross-linguistic generality of the basic effect, while also elucidating
    important language-specific differences in the neurocognitive basis
    of regular and irregular morphological forms.
    BibTeX:
    @article{Walenski2009,
      author = {Matthew Walenski and Katiuscia Sosta and Stefano Cappa and Michael T Ullman},
      title = {Deficits on irregular verbal morphology in Italian-speaking Alzheimer's disease patients.},
      journal = {Neuropsychologia},
      school = {Brain and Language Laboratory, Department of Neuroscience, Georgetown University, Washington, DC 20057-1464, United States. mwalenski@ucsd.edu},
      year = {2009},
      volume = {47},
      number = {5},
      pages = {1245--1255},
      url = {http://dx.doi.org/10.1016/j.neuropsychologia.2008.12.038},
      doi = {http://doi.org/10.1016/j.neuropsychologia.2008.12.038}
    }
    
    Ahmed, F., Tessarollo, L., Thiele, C. & Mocchetti, I. Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain. 2008 Brain Res
    Vol. 1227, pp. 1-11School: Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA. 
    DOI URL 
    Abstract: Chemokine receptors, and in particular CXCR4 and CCR5 play a key role
    in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV)4
    associated dementia (HAD). Thus, new insight into the expression
    of CXCR4 in the central nervous system may help develop therapeutic
    compounds against HAD. Brain-derived neurotrophic factor (BDNF) is
    neuroprotective in vitro against two strains of the HIV envelope
    protein gp120 that binds to CXCR4 or CCR5. Therefore, we examined
    whether BDNF modulates chemokine receptor expression in vivo. The
    content of CXCR4 mRNA and proteins was determined in the cerebral
    cortex and hippocampus of 6-month-old BDNF heterozygous mice and
    wild type littermates by using polymerase chain reaction and immunohistochemistry,
    respectively. BDNF heterozygous mice exhibited an increase in CXCR4
    mRNA compared to wild type. Histological analyses revealed an up-regulation
    of CXCR4 immunoreactivity mainly in neurons. Most of these neurons
    were positive for TrkB, the BDNF receptor with a tyrosine kinase
    activity. Increases in CXCR4 mRNA levels were observed in 18-month-old
    BDNF heterozygous mice but not in 7-day-old mice, suggesting that
    the modulatory role of BDNF occurs only in mature animals. To determine
    whether BDNF affects also CXCR4 internalization, SH-SY5Y neuroblastoma
    cells were exposed to BDNF and cell surface CXCR4 levels were measured
    at various times. BDNF induced CXCR4 internalization within minutes.
    Lastly, BDNF heterozygous mice showed higher levels of CCR5 and CXCR3
    mRNA than wild type in the cerebral cortex, hippocampus and striatum.
    Our data indicate that BDNF may modulate the availability of chemokine
    receptors implicated in HIV infection.
    BibTeX:
    @article{Ahmed2008,
      author = {Farid Ahmed and Lino Tessarollo and Carol Thiele and Italo Mocchetti},
      title = {Brain-derived neurotrophic factor modulates expression of chemokine receptors in the brain.},
      journal = {Brain Res},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA.},
      year = {2008},
      volume = {1227},
      pages = {1--11},
      url = {http://dx.doi.org/10.1016/j.brainres.2008.05.086},
      doi = {http://doi.org/10.1016/j.brainres.2008.05.086}
    }
    
    Bachis, A., Cruz, M.I., Nosheny, R.L. & Mocchetti, I. Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex. 2008 Neurosci Lett
    Vol. 442(2), pp. 104-108School: Department of Neuroscience Georgetown University Medical Center, EP04, New Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, United States. 
    DOI URL 
    Abstract: Stress-mediated loss of synaptogenesis in the hippocampus appears
    to play a role in depressive and mood disorders. However, little
    is known about the effect of stress/depression on the plasticity
    and survival of cortical neurons. In this report, we have examined
    whether chronic stress increases the vulnerability of neurons in
    the rat cortex. We have used a chronic unpredictable mild stress
    (CMS) as a rat model of depression. CMS (5 weeks treatment) produced
    anedonia and increased corticosterone levels. These effects were
    accompanied by a detectable increase in caspase-3 positive neurons
    in the cerebral cortex, suggesting apoptosis. Desipramine (DMI),
    a well known antidepressant, reversed the pro-apoptotic effect of
    CMS. These results suggest that antidepressants may reduce the pathological
    changes seen in stress-induced depressive disorders.
    BibTeX:
    @article{Bachis2008a,
      author = {Alessia Bachis and Maria Idalia Cruz and Rachel L Nosheny and Italo Mocchetti},
      title = {Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex.},
      journal = {Neurosci Lett},
      school = {Department of Neuroscience Georgetown University Medical Center, EP04, New Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, United States.},
      year = {2008},
      volume = {442},
      number = {2},
      pages = {104--108},
      url = {http://dx.doi.org/10.1016/j.neulet.2008.06.081},
      doi = {http://doi.org/10.1016/j.neulet.2008.06.081}
    }
    
    Bachis, A., Mallei, A., Cruz, M.I., Wellstein, A. & Mocchetti, I. Chronic antidepressant treatments increase basic fibroblast growth factor and fibroblast growth factor-binding protein in neurons. 2008 Neuropharmacology
    Vol. 55(7), pp. 1114-1120School: Department of Neuroscience, Georgetown University Medical Center, EP04, New Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USA. 
    DOI URL 
    Abstract: One of the mechanisms proposed for antidepressant drugs is the enhancement
    of synaptic connections and plasticity in the hippocampus and cerebral
    cortex. Fibroblast growth factor 2 (FGF2) is a growth factor essential
    for the proper formation of synaptic connections in the cerebral
    cortex, maturation and survival of catecholamine neurons, and neurogenesis.
    In this report, we attempted to establish a correlation between antidepressant
    treatments and FGF2 expression in the cerebral cortex and hippocampus,
    two brain areas relevant for depression. Desipramine (DMI, 10mg/kg)
    or fluoxetine (FLU, 5mg/kg) was injected acutely (single injection)
    or chronically (daily injection for two weeks) in adult rats. Chronic,
    but not acute, antidepressant treatments increase FGF2 immunoreactivity
    in neurons of the cerebral cortex and in both astrocytes and neurons
    of the hippocampus. FGF2 immunoreactivity in the cortex was increased
    mainly in the cytoplasm of neurons of layer V. Western blot analyses
    of nuclear and cytosolic extracts from the cortex revealed that both
    antidepressants increase FGF2 isoforms in the cytosolic extracts
    and decrease accumulation of FGF2 immunoreactivity in the nucleus.
    To characterize the anatomical and cellular specificity of antidepressants,
    we examined FGF-binding protein (FBP), a secreted protein that acts
    as an extracellular chaperone for FGF2 and enhances its activity.
    DMI and FLU increased FBP immunoreactivity in both cortical and hippocampal
    neurons. Our data suggest that FGF2 and FBP may participate in the
    plastic responses underlying the clinical efficacy of antidepressants.
    BibTeX:
    @article{Bachis2008,
      author = {Alessia Bachis and Alessandra Mallei and Maria Idalia Cruz and Anton Wellstein and Italo Mocchetti},
      title = {Chronic antidepressant treatments increase basic fibroblast growth factor and fibroblast growth factor-binding protein in neurons.},
      journal = {Neuropharmacology},
      school = {Department of Neuroscience, Georgetown University Medical Center, EP04, New Research Building, 3970 Reservoir Road, NW, Washington, DC 20057, USA.},
      year = {2008},
      volume = {55},
      number = {7},
      pages = {1114--1120},
      url = {http://dx.doi.org/10.1016/j.neuropharm.2008.07.014},
      doi = {http://doi.org/10.1016/j.neuropharm.2008.07.014}
    }
    
    Cartagena, C.M., Ahmed, F., Burns, M.P., Pajoohesh-Ganji, A., Pak, D.T., Faden, A.I. & Rebeck, G.W. Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain. 2008 J Neurotrauma
    Vol. 25(9), pp. 1087-1098School: Department of Neuroscience, Georgetown University Medical Center, Washington, D.C. 20057, USA. 
    DOI URL 
    Abstract: In traumatic brain injury (TBI), cellular loss from initial impact
    as well as secondary neurodegeneration leads to increased cholesterol
    and lipid debris at the site of injury. Cholesterol accumulation
    in the periphery can trigger inflammatory mechanisms while cholesterol
    clearance may be anti-inflammatory. Here we investigated whether
    TBI altered the regulation of cholesterol 24S-hydroxylase (Cyp46),
    an enzyme that converts cholesterol to the more hydrophilic 24S-hydroxycholesterol.
    We examined by Western blot and immunohistochemistry changes in Cyp46
    expression following fluid percussion injury. Under normal conditions,
    most Cyp46 was present in neurons, with very little measurable in
    glia. Cyp46 levels were significantly increased at 7 days post-injury,
    and cell type specific analysis at 3 days post-injury showed a significant
    increase in levels of Cyp46 (84 in microglia. Since 24-hydroxycholesterol
    induces activation of genes through the liver X receptor (LXR), we
    examined protein levels of ATP-binding cassette transporter A1 and
    apolipoprotein E, two LXR regulated cholesterol homeostasis proteins.
    Apolipoprotein E and ATP-binding cassette transporter A1 were increased
    at 7 days post-injury, indicating that increased LXR activity coincided
    with increased Cyp46 levels. We found that activation of primary
    rat microglia by LPS in vitro caused increased Cyp46 levels. These
    data suggest that increased microglial Cyp46 activity is part of
    a system for removal of damaged cell membranes post-injury, by conversion
    of cholesterol to 24-hydroxycholesterol and by activation of LXR-regulated
    gene transcription.
    BibTeX:
    @article{Cartagena2008,
      author = {Casandra M Cartagena and Farid Ahmed and Mark P Burns and Ahdeah Pajoohesh-Ganji and Daniel T Pak and Alan I Faden and G. William Rebeck},
      title = {Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain.},
      journal = {J Neurotrauma},
      school = {Department of Neuroscience, Georgetown University Medical Center, Washington, D.C. 20057, USA.},
      year = {2008},
      volume = {25},
      number = {9},
      pages = {1087--1098},
      url = {http://dx.doi.org/10.1089/neu.2007.0444},
      doi = {http://doi.org/10.1089/neu.2007.0444}
    }
    
    Forcelli, P.A. & Heinrichs, S.C. Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring. 2008 Addict Biol
    Vol. 13(1), pp. 52-62School: Department of Psychology, Boston College, USA. 
    DOI URL 
    Abstract: If neurotransmitter balance is upset in the developing nervous system
    by exposure to antidepressant drugs, structural and functional hedonic
    phenotypes of offspring may be affected. In order to test this hypothesis,
    two groups of pregnant Wistar dams were exposed to vehicle or fluoxetine
    by implantation on gestational day 14 of osmotic minipumps delivering
    0 or 10 mg/kg/day fluoxetine for 14 days. The consequences of perinatal
    fluoxetine exposure on offspring conflict-exploratory behavior were
    quantified using the elevated plus-maze on postnatal day (PND) 30.
    Beginning on PND 60, the reinforcing properties of acutely administered
    cocaine were examined using a place conditioning procedure. Beginning
    on PND 90, a subset of rats were implanted with jugular catheters
    and allowed to acquire self-administration of cocaine in an operant
    environment. In support of the hedonic modulation hypothesis, perinatal
    fluoxetine produced a significant decline in both nucleus accumbens
    cell count (-9 and serotonin transporter-like immunoreactivity
    in the raphe nucleus (-35 on PND 120. In the elevated plus-maze,
    perinatal fluoxetine exposure decreased (-21 overall activity.
    In the place conditioning trial, only the fluoxetine-treated group
    exhibited a significant place preference for the compartment paired
    previously with cocaine. In a cocaine self-administration extinction
    trial, there was a statistically significant increase (350 in
    extinction response rate among fluoxetine-exposed offspring. These
    findings suggest that perinatal exposure to fluoxetine perturbs adult
    serotonergic neurotransmission and produces a positive hedonic shift
    for conditioned reinforcing effects of cocaine.
    BibTeX:
    @article{Forcelli2008,
      author = {Patrick A Forcelli and Stephen C Heinrichs},
      title = {Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring.},
      journal = {Addict Biol},
      school = {Department of Psychology, Boston College, USA.},
      year = {2008},
      volume = {13},
      number = {1},
      pages = {52--62},
      url = {http://dx.doi.org/10.1111/j.1369-1600.2007.00078.x},
      doi = {http://doi.org/10.1111/j.1369-1600.2007.00078.x}
    }
    
    Giordano, J. Maldynia: chronic pain as illness, and the need for complementarity in pain care.