~b22 neural mechanisms of learning & memory
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Neural Mechanisms
of Learning& Memory
Lecture 22
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Neural Mechanism of Memory
Short-term Memory
Change inneuralactivity
Reverberatory Circuits
Long-Term Memory
structural change in brain
Hebb Synapse simultaneous activity inpre- &
postsynaptic neurons ~
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Neural Plasticity
Nervous System is malleable
learningoccurs
Structural changes at synapses Changes in synaptic efficiency
Long-term potentiation (LTP)
Long-term depression (LTD) Studied inhippocampus ~
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Inducing LTP
Stimulating
electrodeRecord
PresynapticNeuron PostynapticNeuron
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-70mv
-
+
Postsynaptic Potential
Single elec. stimulation
100 Hz. burst
Single stim.
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LTP Duration
Inhumans: years
Experimentally-induced LTP
Strong,high frequency stimulation
100 Hz
Intact animals
seconds - months
HC slice
40 hrs ~
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LTP: Molecular Mechanisms
Presynaptic & Postsynaptic changes
HC: Glutamate
excitatory
2 postsynaptic receptor subtypes
AMPA-R Na+
NMDA-R
Ca++
Glu NT for both ~
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NMDA Receptor
N-methyl-D-aspartate
chemically-gated
voltage-gated Activation requires
Membrane depolarizationand
Glu bound to receptor~
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Single Action Potential
Glu AMPA-R
Na+ influx
depolarization
Glu NMDA-R
does not open
Mg++ blocks channel no Ca++ intopostsynaptic cell
Followed by more APs ~
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Activation of NMDA-R
Postsynaptic membrane depolarized
Mg++ dislodged
Glu bindingopens channel
Ca++ influx post-synaptic changes
strengthens synapse ~
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AMPA NMDAMg
G
Ca++Na+
G G
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NMDAMg
G
Ca++
GAMPA
Na+
G
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NMDA
MgG G
Ca++
AMPA
Na+
G
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NMDAG
Ca++
G
Mg
AMPA
Na+
G
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LTP: Postsynaptic Changes
Receptor synthesis
More synapses
Shape of dendritic spines Nitric Oxide synthesis ~
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Presynaptic
Axon Terminal
Dendritic
Spine
Before LTP
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Nitric Oxide - NO
Retrograde messenger
Hi conc. poisonous gas
Hi lipid solubility
storage?
Synthesis on demand
Ca++ N
O synthase N
O Increases NT synthesis inpresynaptic
neuron
more released during AP ~
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G
Ca++
G
Ca++NOSNO
NO Glu
G
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Long-term Depression: Hippocampus
Decreased synaptic efficiency
Forgetting?
Glutamamte-R
AMPA-R & NMDA-R
Stimulationpattern?
1Hz for10-15 min
Low Ca++ influx
Decrease # of AMPA-R
Weaker EPSPs ~
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Hippocampus: LTP vs LTD
Same receptors
Different stimulation frequency
Different Ca++ concentrations LTD can reverse LTP
LTP can reverse LTD
Similar mechanisms inotherareas Not necessarily identical ~