Neuroscience Module 1  -  2008

Barry Wolfe

Learning Objectives

Receptors and Signal Transduction

 

1.  What are efficacy and potency from the point of view of a dose-response curve?

From a molecular point of view?  What are Kd, EC50, Ki, IC50, and Bmax? What is a partial agonist?  What are the mechanistic and kinetic differences between competitive and noncompetitive antagonists?  What is t1/2?  How long does it take to clear >90% of a drug?  How long does it take to reach >90% of steady state concentrations?

 

2.  What are the functional and temporal differences between GPCR signaling and ligand-gated ion channel signaling?  What are the structural differences between the two types of receptors?  What is the difference between subunits and subtypes of receptors?   What is a G protein and how does GPCR-stimulated G protein signal transduction work on a molecular level.  What are the ‘turn on’ and ‘turn off’ steps for all G protein signaling?   How is cyclic AMP synthesized, what does it do, how is its action terminated?

 

3. What are the functional and binding domains of GPCRs?  What are the structural differences between the three types of GPCR?   What evidence is there that at least some GPCRs dimerize and that this dimerization is necessary for function?

 

4.  What are the characteristics of the three classes of adenylyl cyclase?

 

5.  What do cholera toxin and pertussis toxin do?  Which G protein is each specific for and what is the functional consequence of treating cells or a tissue with one of these toxins?

 

6.  How does desensitization of the b-adrenergic receptor occur?  (i.e. what are the molecular events)

 

7.  How does PLC signaling work at the molecular level?  i.e. What substrate is involved and which second messengers are generated and what do these second messengers do?  What G protein(s) are involved.  Why is PLC signaling sensitive to pertussis toxin in some tissues/cells and in others not - and sometimes only partially in the same cell?

 

8.  What is the general motif for regulating the protein kinases we discussed (inhibition by regulatory proteins or polypeptides).  What amino acids are targets for phosphorylation?  Why?  What classes of kinases are there (Y and S/T)?  What does it mean that a kinase has a consensus sequence?

 

9.  What are cognitive kinases and how do each of them manage to stay stimulated and 'remember' that they have been stimulated recently?

 

10.   What types of phosphatases are there?  (S/T vs Y  -  second messenger regulated vs constituitive).  How is DARPP-32 regulated and what does it regulate?


 

 

Neurotransmitter Pathways and Presynaptic Mechanisms in Neurotransmission

Ken Kellar

Learning Objectives

 

The objectives of the next two lectures are to provide an overview of the major neurotransmitters Acetylcholine, Norepinephrine, Dopamine, Serotonin, GABA and Glutamate in the central and peripheral nervous systems.  Your goals should be to gain an understanding of and appreciation for:

 

1) The anatomical distributions of the major neurotransmitters in the CNS and peripheral nervous systems.  

 

2) The known physiological roles of these neurotransmitters in the autonomic nervous system, neuromuscular junction and some of the major pathways in the CNS.

 

3) The apparent roles of neurotransmitters in diseases of the nervous system.

4) The life cycle of the major neurotransmitters:

            A) Synthesis, including the rate limiting steps for each transmitter

            B) Mechanisms that regulate synthesis for each transmitter

            C) Storage of neurotransmitters in preparation for release

            D) The basic steps involved in exocytotic release and alternative mechanisms

            E) The termination of neurotransmitter actions in the synapse

            F) Regulation of neurotransmitter synthesis, release and neuronal firing rate by autoreceptors

            G) Co-transmitters

 

5) Introduction to non-classical neurotransmitters, e.g. nitric oxide (NO)

 

6)  The array of receptor subtypes for the neurotransmitters

 

7)  How drugs are useful both therapeutically and as crucial tools to study neurotransmission.     

 

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Lectures on Transcription Factors

By Dr. Baoji Xu

 

Objectives:

  1. What is a transcription factor?  What is the difference between a transcription factor and a general transcription factor?  What is the role of transcription in the development and function of the nervous system?
  2. What is a domain in a protein?  What common domains does a transcription factor have?  What is the function of each domain?
  3. How does a transcription factor activate or repress gene expression?  What are histone acetylation and deacetylation?  What are their roles in the control of gene expression?
  4. How does an extracellular signal induce expression of a transcription factor or activate pre-existing transcription factors?
  5. Why is the regulation of gene expression by neuronal activity important to the nervous system?
  6. What do we know about the mechanisms by which neuronal activity induces gene expression?
  7. What is the molecular basis of Rett Syndrome?
  8. Know common techniques used in the field: Northern blot, Western blot, chromatin immunoprecipitation, electrophoretic mobility shift assay, reporter assay, co-immunoprecipitation.