read Ch 6,7  in Dudai!!! ; Schacter Ch 11 ; Fazelli & Collingridge, 1996 ; extra small print is for your information but will not be tested
Nov 24
Overview of synaptic transmission:
  1. Process -  we are  using the total sodium influx through postsynaptic AMPA channels as our measure of synaptic efficacy. Therefore, synaptic modifications could be the result of changes in
    1. Presynaptic process
      1. moving of vesicles from storage to releasable pool
      2. protiens (amino acids) involved in releasing vesicles: structural/enzymatic (serine/threonine and tyrosine kinases/phosphotases).
    2. reuptake or degradation of glutamate
    3. postsynaptic processes
      1. protiens (amino acids) involved in producing a AMPA mediated response: structural/enzymatic (serine/threonine and tyrosine kinases/phosphotases).
      2. phosphorylation of AMPA receptor
I. Mechanisms:
  1. Levels of activity:
    1. Postsynaptic depolarization -
    2. Level of intracellular calcium -
    3. Level of AMPA phosphorylation
    4. LTD/LTP curve
Dec 1
IV Specifics/Exceptions
  1. Calcium increase:
    1. NMDA receptor- requires 1) depolarization to remove Mg2+ block and 2) glutamate binding:  heteromeric assembliy of subunits encoded by 5 separate genes. NR1,2A-D. NR1 is essential for proper functioning. NR$ influences fundamental properties such as voltage dependence of Mg block, the CA2+ permeability, regulation by phosphorylation and channel kinetics. NR1 exists in 8 alternatively spliced bariants and truncated short form.
    2. Voltage dependent calcium channels
    3. IP3 receptors - EM or spine apparatus
  2. Protein syntheis dependent expression of change in synaptic strength:- Kandel article
    1. change in 2nd messenger concentration or ratio of catalytic/regulatory
    2. change in spine shape
    3. change in #  of AMPA receptors at the synapse
  3. Protein synthesis independent expression of change in synaptic strength: modification of pre-existing proteins - Lisman hypothesis
    1. AMPA receptor phosphorylation:
      1. Structure: heteromeric assembly of subunits (probably a pentamer). Subunits are encoded by four separate enes (GluR1-4).  Absence of GluR2 subunit confers significant Ca permeability to AMPA receptors. Each of the four genes can encode one of two spice variants termed 'flip' and 'flop'  which form channels with different conductance properties. RNA editing also can impart diversity upon the receptor.  Editing of GluR2 by RNA adenosine deaminase will limit the calcium permeability of the receptor.
      2. Phosphorylation by activated CaCMKII
  1. retrograde messengers: evidence for this process comes from 1) quantal analysis, 2) double impalements.  Nitic oxide (NO), carbon monoxide (CO), arachidonic acid (AA) and platelet-activating factor (PAF).  NO is a free radical produced by nitric oxide synthase (neuronal form and enothelial form NOS) during the oxidation of arginine to citrulline.  NOS is stmulated by calcium and calmodulin allowing the NO signal to be coupled to increases in intracellular calcium. NO stimulates the production of cGMP & cGMP dependent protein kinase (PKG) through the activation of gyanylyl cyclase.
PECULIARITIES
  1. mossy fiber - CA3 LTP is entirely a presynaptic phenomenon
  2. Cerebellum - LTP is not produced by activation of NMDA receptors
V. Conclusions:
Implicit and Explicit memory formation probably share the same mechanism.  The main difference is 1. Where the storage takes place and 2) what factors lead to the induction of the changes.