Neural Mechanisms of Learning Memory Lesson 24 Neural

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Neural Mechanisms of Learning & Memory Lesson 24

Neural Mechanisms of Learning & Memory Lesson 24

Neural Mechanism of Memory Short-term Memory l Change in neural activity l Reverberatory Circuits

Neural Mechanism of Memory Short-term Memory l Change in neural activity l Reverberatory Circuits n Long-Term Memory l structural change in brain l Hebb Synapse l simultaneous activity in pre- & postsynaptic neurons ~ n

Neural Plasticity Nervous System is malleable l learning occurs l Structural changes at synapses

Neural Plasticity Nervous System is malleable l learning occurs l Structural changes at synapses n Changes in synaptic efficiency l Long-term potentiation (LTP) l Long-term depression (LTD) n Studied in hippocampus l and other places ~ n

Inducing LTP Stimulating electrode Presynaptic Neuron Record Postynaptic Neuron

Inducing LTP Stimulating electrode Presynaptic Neuron Record Postynaptic Neuron

Postsynaptic Potential Single elec. stimulation + -70 mv - 100 Hz. burst Single stim.

Postsynaptic Potential Single elec. stimulation + -70 mv - 100 Hz. burst Single stim.

LTP Duration In humans: years n Experimentally-induced LTP l Strong, high frequency stimulation l

LTP Duration In humans: years n Experimentally-induced LTP l Strong, high frequency stimulation l 100 Hz n Intact animals l seconds - months n HC slice l 40 hrs ~ n

LTP: Molecular Mechanisms Presynaptic & Postsynaptic changes n HC: Glutamate l excitatory n 2

LTP: Molecular Mechanisms Presynaptic & Postsynaptic changes n HC: Glutamate l excitatory n 2 postsynaptic receptor subtypes l AMPA-R Na+ l NMDA-R Ca++ n Glu NT for both ~ n

NMDA Receptor N-methyl-D-aspartate l chemically-gated l voltage-gated n Activation requires l Membrane depolarization and

NMDA Receptor N-methyl-D-aspartate l chemically-gated l voltage-gated n Activation requires l Membrane depolarization and l Glu bound to receptor~ n

Single Action Potential Glu AMPA-R l Na+ influx l depolarization n Glu NMDA-R l

Single Action Potential Glu AMPA-R l Na+ influx l depolarization n Glu NMDA-R l does not open l Mg++ blocks channel l no Ca++ into postsynaptic cell n Followed by more APs ~ n

Activation of NMDA-R Postsynaptic membrane depolarized l Mg++ dislodged l Glu binding opens channel

Activation of NMDA-R Postsynaptic membrane depolarized l Mg++ dislodged l Glu binding opens channel n Ca++ influx post-synaptic changes l strengthens synapse ~ n

Ca++ Na+ AMPA G G G Mg NMDA

Ca++ Na+ AMPA G G G Mg NMDA

Ca++ Na+ AMPA G G G Mg NMDA

Ca++ Na+ AMPA G G G Mg NMDA

Na+ AMPA G Mg G Ca++ G NMDA

Na+ AMPA G Mg G Ca++ G NMDA

AMPA Ca++ Mg Na+ G G G NMDA

AMPA Ca++ Mg Na+ G G G NMDA

LTP: Postsynaptic Changes Receptor synthesis n More synapses n Shape of dendritic spines n

LTP: Postsynaptic Changes Receptor synthesis n More synapses n Shape of dendritic spines n Nitric Oxide synthesis ~ n

Before LTP Presynaptic Axon Terminal Dendritic Spine

Before LTP Presynaptic Axon Terminal Dendritic Spine

After LTP Presynaptic Axon Terminal less Fodrin Less resistance Dendritic Spine

After LTP Presynaptic Axon Terminal less Fodrin Less resistance Dendritic Spine

Nitric Oxide - NO Retrograde messenger l Hi conc. poisonous gas n Hi lipid

Nitric Oxide - NO Retrograde messenger l Hi conc. poisonous gas n Hi lipid solubility l storage? n Synthesis on demand l Ca++ NO synthase NO n Increases NT synthesis in presynaptic neuron l more released during AP ~ n

Glu NO G NO NOS Ca++ G G Ca++

Glu NO G NO NOS Ca++ G G Ca++

Long-term Depression: Hippocampus Decreased synaptic efficiency l Forgetting? n Glutamamte-R l AMPA-R & NMDA-R

Long-term Depression: Hippocampus Decreased synaptic efficiency l Forgetting? n Glutamamte-R l AMPA-R & NMDA-R n Stimulation pattern? l 1 Hz for 10 -15 min l Low Ca++ influx n Decrease # of AMPA-R l Weaker EPSPs ~ n

Hippocampus: LTP vs LTD Same receptors l Different stimulation frequency l Different Ca++ concentrations

Hippocampus: LTP vs LTD Same receptors l Different stimulation frequency l Different Ca++ concentrations n LTD can reverse LTP n LTP can reverse LTD n Similar mechanisms in other areas l Not necessarily identical ~ n