Table of Contents
Synaptic Plasticity and Memory
Synaptic Plasticity and Memory (SPM) Hypothesis
Synaptic Plasticity and the Memory Hypothesis - Logical Criteria:
Synaptic memory: as a realistic Memory Device?
Natural Stimulation can induce SP
Carbachol (CCh = Ach agonist) in Slices induces Theta Activity
Single Burst (4 shocks at 100 Hz) delivered at peak of the theta oscillation induces LTP
Input Specificity of ? LTP
Reliability of ? LTP (mean of several animals)
Induction of ? LTD
? LTD with burst during trough of Theta oscillation
Bi-directionality of ? LTP and ? LTD
Experimental Strategies to test Synaptic Plasticity (SP) = Memory?
How Experimental Strategies relate to the 4 logical criteria of the SPM
Correlation - Memory and SP
Induction: Fear Memory in Amygdala
Occlusion - Does Saturation of SP (LTP) impair Memory?
Occlusion Strategy
Occlusion Strategy
Occlusion Stragegy
Occlusion Stragegy Test saturated LTP block of Memory
Occlusion - Saturation Mechanism
Intervention Strategy NMDAR blockade and Memory
Intervention - AP5 block of NMDAR
Intervention Does enhancement of LTP result in better Learning and Memory?
Pharmacologically Enhanced LTP
Over-expression of NR2B in transgenic mouse
PSD-95 mutant mouse
Erasure - idea
Evidence for Behavioral Erasure of LTP
Novel Environment Erases LTP produced in the Familiar Environment (FE)
Little or No effect of Handling on LTP in FE
Experiments to test Erasure induced by LTP over-riding a learned network
Experimental Paradigm
Electrodes - stimulation protocols
Normal learning and retention during training without electrical stimulation
HF stim 2 hr after Retention test 1 produces LTP and erases memory for target location in the HF animals
Genetic Intervention and Erasure
Intervention Strategy - methods iCA1-KO mouse
Intervention Strategy - methods
CA1 specificity of NMDA transgene expression
Adding Doxy blocks NR1-GFP expression in area CA1
NMDA currents absent in iCA1-KO with doxy in the water - in slices
LTP blocked in iCA1-KO (doxy)
Absent NMDAr (iCA1-KO,doxy) impairs learning on Morris Water Maze
Target location preference also impaired in absence of NMDAr
Preventing NMDAr expression immediately after training
Preventing NMDAr expression long after training
Implications
Implications, cont.
Progress in testing Synaptic Plasticity Memory (SPM) Hypothesis
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