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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 ~