Neural Mechanisms of Learning & Memory Lesson 24

Neural Mechanism of Memory n 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 ~

Neural Plasticity n 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 ~

Inducing LTP Stimulating electrode Record Presynaptic Neuron Postynaptic Neuron

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

LTP Duration n 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 ~

LTP: Molecular Mechanisms n 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 ~

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

Single Action Potential n 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 ~

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

AMPA NMDA Mg G Ca++ Na+ G G

NMDA Mg G Ca++ G AMPA Na+ G

NMDA Mg GG Ca++ AMPA Na+ G

NMDA G Ca++ G Mg AMPA Na+ G

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

Presynaptic Axon Terminal Dendritic Spine Before LTP

Presynaptic Axon Terminal Dendritic Spine After LTP less Fodrin Less resistance

Nitric Oxide - NO n 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 ~

G Ca++ G NOSNO Glu G

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

Hippocampus: LTP vs LTD n 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 ~