Tuesday, March 25, 2014 CC-BY-NC
Synaptic plasticity

Maintainer: admin


  • synaptic plasticity:
    • changes in strength of a connection based on recent firing patterns and modulatory transmitters
  • functions in

    • learning and memory: experiences
    • homeostasis : keep the overall excitability of a neuron
    • mood and behaviour : alertness, different effect of the same stimuls at different time
  • strenght of a synapse(M) = NPQ

    • P : probability of release of a synaptic vesicle after an action potential
    • Q : amplitude of the post-synaptic potential (PSP) due to release of one vesicle
    • N : number of synapses or vesicle release spots

2Regulation of P

  • amount of calcium
  • number of readily releasable vesicles
    • readily releasable pool (RRP) can be measured with hypertonic shock with sucrose
    • this would simultaneously fuse all primed vesicles -> can measure RRP
  • coupling of calcium entry to fusion of vesicles

  • also modulated by

    • recent firing patterns -> paired pulse plasticity
    • modulatory neurotransmission
      • ex: short-term facilitation in aplysia
    • long-term potentiation
      • induced by PKA
      • have to do with Rab3A and phosphoryation of RIM

3Paired Pulse plasticity

  • def: a change in probabilty of a vesicle fusing when two action potentials occur in succession
  • depends on the time in between pulses
  • due to residual calcium

    • saturate the endogenous calcium buffers to that new calcium entering shortly afterwards gives rise to a higher concentration.
  • Types (not memory formation, because transient)

    • paired pulse facilitation
      • second postsynpatic action potential is stronger than the first
      • if p was small for the first action potential
    • paire pulse depression
      • second postsynpatic action potential is weaker than the first
      • if p was large for the first action potential ; more RRP was secreted
        • not enough time to regenerate the vesicles,
    • post-tetanic potentiation
      • tetanic: high freqency action potential
      • will get depression first
      • wait a few minutes and then fire action potential : get facilitation
      • after short burst of action potential, there's an increase in p because:
        • residual calcium binds to calcium sensors
        • residual calcium persists because they can leak out of mitochondria after being reuptake

3.1Regulation of

  • Munc 13 : calcium dependent increase in RRP :

    • not only remove inhibitory effect of Munc18 on Syntaxin
    • but also binds to calmodulin, a calcium senseor
    • when the calmodulin-binding domain is removed, PTP is reduced
      • no calcium-induced increase in RRP
  • Unc 13

    • regultory hub for priming
    • DAG, produced by phospholipase C, directly binds to unc13
      • in combination of PKC phosphorylatino of Munc18 increase priming
    • removing C1 domain of unc13 blocks modulation by DAG

4memory formation

  • aplysia, a stupid sea animal, can learn to retract its siphon faster after bieng shock
  • sensitization is due to serotoninergic interneuron
    • serotonin increase synaptic strength in both motor and sensory neurons
  • repeated firing leads to less release and decrease of EPSP to motor neuron
    • RRP is intact
    • depression blocks calcium-secretion coupling
  • whereas, shock removes the desensitization/depression
    • serotonin leads to more release and increase of EPSP to motor neurons
    • does this by PKC regulation

4.1Mechanism of serotonin

  • shock release serotonin (5-HT) from interneuron
  • 5-HT acts through G proein linked receptor and thereby increases cAMP level
  • cAMP activates PKA
  • PKA phosphorylates K+ channels and thereby inactivates them
    • also increases priming in vertebrates via phosphorylation of RIM
  • slow repoloarization -> broadened action potential -> more calcium influx -> more transmitter - > bigger EPSP

4.2Long-term potentiation (LTP)

  • seen at

    • dentate gyrus to CA3
    • parallel fibers to purkinje cells
    • both depends on PKA activation
      • phosphorylates RIM and K+ channels
    • both are gone in Rab3A or RIM knockouts
  • experiment on RIM

    • replaces phosphorylated site with other amino acids
    • lack of rescue with phosphorylation suggest phosphorylation of RIM is critical for LTP


  • need to know :
    • M=NPQ
    • PPF and PTP mechanism, how they relate to p
    • sensitization and associative memories with the changes in p