NSCI-502. Cellular & Molecular Neuroscience / In-Depth

NSCI 502 Fall 2007  -  Cell Biology of the Synapse                 close window  
Wednesdays  -  1:00 -4:00 in NE401 Med/Dent                                 

Module 1   Inhibition in the CNS  -  Molly Huntsman    mh257@georgetown.edu

September 5, 2007:   Overview:   Funtional inhibitory circuits:  The basics of GABAA receptors and GABA neurons

1. .  This is a review class for sessions 2-4 in the lecture style format but reading both reviews will help you follow along and understand the next 3 sessions

Read these reviews before class meets

1.  Fundamental Reviews: Markram et al. 2004,  Interneurons of the neocortical inhibitory system.   Nature Reviews 5:793.

2. Mody and Pearce, 2004, Diversity of inhibitory neurotransmission through GABAA receptors.  Trends in Neurosci. 27:569-575

3.  Recent review: Fritschy and Brunig, 2003, Formation and Plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications (skip sections 3 and 4). Pharmacology and Therapeutics 98: 299-323.

September 12, 2007 : Where do GABA neurons come from?  What is GABA doing in the developing brain?

Main Papers to Read:
 
1.  Miyoshi , Butt , Takebayashi and Fishell 2007, Physiologically distinct temporal cohorts of cortical interneurons arise from telencephalic Olig2-expressing precursors. J Neurosci. 27:7786

2.  Akerman and Cline 2006, Depolarizing GABAergic Conductances Regulate the Balance of Excitation to Inhibition in the Developing Retinotectal Circuit In Vivo  J Neurosci 26:5117-30

3.  Review:  Akerman and Cline 2007, Refining the roles of GABAergic signaling during neural circuit formation. Trends Neurosci. 30 :382

 September 19, 2007 :  What's location got to do with it?   Extra-synaptic GABAA receptors: what do they do and how are they controlled?

Main Papers to Read:

1.  Zhang, Wei, Mody and Houser, 2007 Altered localization of GABA(A) receptor subunits on dentate granule cell dendrites influences tonic and phasic inhibition in a mouse model of epilepsy. J Neurosci 27:7520

2.  Review:   Semyanov et al. Tonically active GABAa receptors: Modulating gain and maintaining the tone. Trends Neurosci. 27: 262 (2004)

September 26, 2007 :  Inhibitory neurons in action!    How do they control themselves and others in intact circuits?

1.  Pouille and Scanziani 2001, Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition. Science 293:1159.

2. Katagiri, Fagiollini and Hensch 2007. Optimization of Somatic Inhibition at Critical Period Onset in Mouse Visual Cortex  Neuron53: 805.

3.  Review:  Bacci, Huguenard and Prince 2005, Modulation of Neocortical interneurons: extrinsic influences and exercises in self control. Trends Neurosci 28: 602

Module 2   -  Synaptic Plasticity  -   Barry Wolfe

bwolfe01@georgetown.edu 

October 3, 2007:  How do proteins interact at the synapse?

Main Papers to Read:

1.      PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking.  Neuron 47:407, 2005

2.      Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor Cell 111: 219, 2002

3.   Related paper - But DON'T DO THIS ONE  Regulation of Dopamine D1 receptor trafficking and desensitization by oligomerization with glutamate N-methly-D-aspartate receptors. J.Biol.Chem. 278:20196-20202 (2003).         

Review  Papers:

R1.      Kim and Sheng PDZ Domain Proteins of Synapses.  Nature Reviews Neuroscience 5:771, 2004

R2.   Salter D1 and NMDA receptors hook up:  expanding on an emerging theme.  Trends in Neuroscience 26:235, 2003

October 10, 2007:  Trafficking with NMDA receptors

Main Papers to Read:

1.     NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex. Nature Cell Biology 5:520-530 (2003).

Review  Paper:

R1.      The return of the exocyst. Nature Cell Biology 5:493-495 (2003).

 
 October 17, 2007:   Does LTP or Learning Drive Surface Expression of AMPA  Receptors?

1.     Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Hayashi, Shi, Esteban, Piccini, Poncer and Malinow.  Science 287:2262-2267 (2000).

2.      LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1.  Grosshans, Clayton, Coultrap and Browning.  Nature Neuroscience 5:27-33 (2002).  CONTRAST THIS PAPER WITH PAPER #1

October 24, 2007:    What is a partial agonist?
Main Papers to Read:

1.    Structural basis for partial agonist action at ionotropic glutamate receptors.  Nature Neuroscience 6: 803, 2003

Reviews :  

R1.  Crystalizing our understanding of partial agonists.  Nature Neuroscience 6:788, 2003     

October 31, 2007.   Research the question:  What is the molecular mechanism of desensitization of a ligand or voltage-gated ion channel?

Students pick one paper each that illustrates a MOLECULAR mechanism of desensitization of a ligand- or voltage-gated channel.   Present and discuss one or two figures from your paper that illustrate the mechanism for your channel.

 November 7, 2006.  :    Society for Neuroscience meeting

Module 3   Glutamate Receptors  -  Stefano Vicini               svicin01@georgetown.edu

November 14, 2007.   Which functional glutamate receptors are found on neuronal membranes?
Main Papers to Read:

1.  Forsythe ID, Westbrook GL. Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on cultured mouse central neurones. J Physiol. 1988 Feb;396:515-33. 

2.  Spruston N, Jonas P, Sakmann B. Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. J Physiol. 1995 Jan 15; 482 ( Pt 2):325-52. 

Review  Paper:

Cull-Candy S, Brickley S, Farrant M. NMDA receptor subunits: diversity, development and disease. Curr Opin Neurobiol. 2001 Jun;11(3):327-335. Review.

    
November 28, 2007.   NMDAR heterogeneity-Do NMDA receptors move??
Main Papers to Read:

Tovar KR, Westbrook GL. The incorporation of NMDA receptors with a distinct subunit composition at nascent hippocampal synapses in vitro. J Neurosci. 1999 May 15;19(10):4180-8.

Tovar KR, Westbrook GL Mobile NMDA receptors at hippocampal synapses. Neuron. 2002 Apr 11;34(2):255-64.

December 5, 2007.     KainateR heterogeneity-Are kainate receptors involved in pain??
Main Papers to Read:

Kerchner GA, Wilding TJ, Li P, Zhuo M, Huettner JE. Presynaptic kainate receptors regulate spinal sensory transmission. J Neurosci. 2001 Jan 1;21(1):59-66.

Li P, Wilding TJ, Kim SJ, Calejesan AA, Huettner JE, Zhuo Kainate-receptor-mediated sensory synaptic transmission in mammalian spinal cord. Nature. 1999 Jan 14;397(6715):161-4.

Wilding TJ, Huettner JE. Activation and desensitization of hippocampal kainate receptors. J Neurosci. 1997 Apr 15;17(8):2713-21.


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