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Neural Mechanisms of Learning & Memory. Lecture 22. Neural Mechanism of Memory. Short-term Memory Change in neural activity Reverberatory Circuits Long-Term Memory structural change in brain Hebb Synapse simultaneous activity in pre- & postsynaptic neurons ~. Neural Plasticity. - PowerPoint PPT Presentation
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Neural Mechanismsof Learning & Memory
Lecture 22
Neural Mechanism of Memory
Short-term Memory Change in neural activity Reverberatory Circuits
Long-Term Memory structural change in brain Hebb Synapse simultaneous activity in pre- &
postsynaptic neurons ~
Neural Plasticity
Nervous System is malleable learning occurs Structural changes at synapses
Changes in synaptic efficiency Long-term potentiation (LTP) Long-term depression (LTD)
Studied in hippocampus ~
Inducing LTP
Stimulating electrode
Record
PresynapticNeuron
PostynapticNeuron
-70mv
-
+
Postsynaptic Potential
Single elec. stimulation100 Hz. burstSingle stim.
LTP Duration In humans: years Experimentally-induced LTP
Strong, high frequency stimulation 100 Hz
Intact animals seconds - months
HC slice 40 hrs ~
LTP: Molecular Mechanisms
Presynaptic & Postsynaptic changes HC: Glutamate
excitatory 2 postsynaptic receptor subtypes
AMPA-R Na+ NMDA-R Ca++
Glu NT for both ~
NMDA Receptor
N-methyl-D-aspartate chemically-gated voltage-gated
Activation requires Membrane depolarization and Glu bound to receptor~
Single Action Potential
Glu AMPA-R Na+ influx depolarization
Glu NMDA-R does not open Mg++ blocks channel no Ca++ into postsynaptic cell
Followed by more APs ~
Activation of NMDA-R
Postsynaptic membrane depolarized Mg++ dislodged Glu binding opens channel
Ca++ influx post-synaptic changes strengthens synapse ~
AMPA NMDAMg
G
Ca++Na+
G G
NMDAMg
G
Ca++
GAMPA
Na+
G
NMDA
MgG G
Ca++
AMPA
Na+G
NMDAG
Ca++
G
Mg
AMPA
Na+
G
LTP: Postsynaptic Changes
Receptor synthesis More synapses Shape of dendritic spines Nitric Oxide synthesis ~
PresynapticAxon Terminal
Dendritic Spine
Before LTP
PresynapticAxon Terminal
Dendritic Spine
After LTP
less FodrinLess resistance
Nitric Oxide - NO
Retrograde messenger Hi conc. poisonous gas
Hi lipid solubility storage?
Synthesis on demand Ca++ NO synthase NO
Increases NT synthesis in presynaptic neuron more released during AP ~
G Ca++
G
Ca++NOSNO
NO Glu
G
Long-term Depression: Hippocampus Decreased synaptic efficiency
Forgetting? Glutamamte-R
AMPA-R & NMDA-R Stimulation pattern?
1 Hz for 10-15 min Low Ca++ influx
Decrease # of AMPA-R Weaker EPSPs ~
Hippocampus: LTP vs LTD
Same receptors Different stimulation frequency Different Ca++ concentrations
LTD can reverse LTP LTP can reverse LTD Similar mechanisms in other areas
Not necessarily identical ~