Neural Mechanisms of Learning Memory Lesson 24 Neural

Neural Mechanisms of Learning & Memory Lesson 24

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 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

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 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 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 l Glu bound to receptor~ n

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 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

Na+ AMPA G Mg G Ca++ G NMDA

AMPA Ca++ Mg Na+ G G G NMDA

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

After LTP Presynaptic Axon Terminal less Fodrin Less resistance Dendritic Spine

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++

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 n LTD can reverse LTP n LTP can reverse LTD n Similar mechanisms in other areas l Not necessarily identical ~ n