~BN15 Neural plasticity - LTP.ppt

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  • 1. Neural Plasticity: Long-term Potentiation Lecture 15
  • 2. Neural Plasticity
    • Nervous System is malleable
      • learning occurs
    • Structural changes
      • increased dendritic branching
      • new synapses
    • Changes in synaptic efficiency
      • Long-term potentiation
      • Long-term depression ~
  • 3. Neural Mechanism of Memory
    • Donald Hebb
    • Short-term Memory
      • Change in neural activity
      • not structural
      • temporary
    • Reverberatory Circuits -
      • cortical loops of activity ~
  • 4. Reverberating Loops
    • Maintains neural activity for a period
      • Activity decays ~
  • 5. Hebb’s Postulate
    • Long-Term Memory
      • required structural change in brain
      • relatively permanent
    • Hebb Synapse
      • use strengthens synaptic efficiency
      • concurrent activity required
        • pre- & postsynaptic neurons ~
  • 6. Before LTP
  • 7. After LTP
  • 8. Long-term Potentiation
    • According to Hebb rule
      • use strengthens synaptic connection
    • Synaptic facilitation
      • Structural changes
      • Simultaneous activity
    • Experimentally produced
      • hippocampal slices
      • associative learning also ~
  • 9. Inducing LTP Stimulating electrode Record DG Perforant Pathway
  • 10. -70mv - + Postsynaptic Potential Single elec. stimulation 100 stim. burst Single stim .
  • 11.
    • Strong, high frequency stimulation
    • Minimum stimulation
      • 1 + burst of 4
      • 4-7 Hz
        • Theta
      • HC: Arousal & REM ~
    Pattern Of Stimulation
  • 12. LTP Duration
    • Experimentally-induced LTP
    • Intact animals
      • seconds - months
    • HC slice
      • 40 hrs ~
  • 13. LTP: Molecular Mechanisms
    • Presynaptic & Postsynaptic changes
    • HC  Glutamate
      • excitatory
    • 2 postsynaptic receptor subtypes
      • AMPA  Na+
      • NMDA  Ca++
    • Glu ligand for both ~
  • 14. NMDA Receptor
    • N-methyl-D-aspartate
    • Glu binding opens channel?
      • required, but not sufficient
    • Membrane must be depolarized
      • before Glu binds ~
  • 15. Single Action Potential
    • Glu  AMPA
        •  -amino-3-hydroxyl-5-methyl-4-isoxazole-propionate
      • depolarization
    • Glu  NMDA
      • does not open
      • Mg++ blocks channel
      • no Ca++ into postsynaptic cell
    • Followed by more APs ~
  • 16. NMDA G Ca++ G AMPA Na+ G Mg
  • 17. NMDA G G Ca++ AMPA Na+ G Mg
  • 18. NMDA G Ca++ G AMPA Na+ G Mg
  • 19. Activation of NMDA-R
    • Ca++ channel
      • chemically-gated
      • voltage-gated
        • Mg++ blocks channel
    • Ca++ influx  post-synaptic changes
      • strengthens synapse ~
  • 20. LTP: Postsynaptic Changes
    • Receptor synthesis
    • More synapses
    • Shape of dendritic spines
    • Nitric Oxide synthesis ~
  • 21. Presynaptic Axon Terminal Dendritic Spine Before LTP
  • 22.
    • less Fodrin
    • Less resistance
    Presynaptic Axon Terminal Dendritic Spine After LTP
  • 23. 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 ~
  • 24. G Ca++ G Ca++ NO G NOS NO cGMP Glu