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Neural Mechanisms of Learning & Memory

Neural Mechanisms of Learning & Memory. Lesson 24. 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.

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Neural Mechanisms of Learning & Memory

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  1. Neural Mechanismsof Learning & Memory Lesson 24

  2. 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 ~

  3. 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 • and other places ~

  4. Inducing LTP Stimulating electrode Record PresynapticNeuron PostynapticNeuron

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

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

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

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

  9. 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 ~

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

  11. Mg Ca++ Na+ G G G AMPA NMDA

  12. Mg Ca++ Na+ G G G AMPA NMDA

  13. Mg Ca++ Na+ G G G AMPA NMDA

  14. Mg Ca++ Na+ G G G AMPA NMDA

  15. LTP: Postsynaptic Changes • Receptor synthesis • More synapses • Shape of dendritic spines • Nitric Oxide synthesis ~

  16. Before LTP Presynaptic Axon Terminal Dendritic Spine

  17. After LTP less Fodrin Less resistance Presynaptic Axon Terminal Dendritic Spine

  18. 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 ~

  19. Glu NO NOS NO Ca++ G G G Ca++

  20. 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 ~

  21. 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 ~

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