Neural Mechanisms of Learning & Memory

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 ~