Home NEUR 310 Thursday, April 3, 2014

Thursday, April 3, 2014 CC-BY-NC
Synaptic plasticity part 3

Maintainer: admin

1LDP (long term depression)

  • Hebb: when neuron A repeatedly failre to excite a post-synaptic neuron B while the other neurons excite B, A and B's connection weakens

  • two properties

    • heterosynaptic : one synapse strengthen and one weakens
    • associative: firing asynchronously and the one with stronger stimulation strengthens while the other one weakens

  • weak prolonged stimulation can lead to homosynaptic LTD

    • ex: 1Hz stimulus, eventually brings down the EPS amplitude
  • homosynaptic LTD : input specific
  • LTD requires NMDA-R activation and maybe Ca+ influx, but not CamKII
    • instead it requires protein phosphatase
    • evidence : inhibiting PP1 and PP2B (calcineurin) using okadaic acid leads to no LTD

1.1Mechanism

  • LTD is due to endocytosis of AMPA receptors

    • low ca+ binds to high ca+ affinity protein phosphatase instead of low ca+ affinity PKC and CamKII
    • protein phosphatase dephosphorylate some substrates and lead to internalization of AMPA-Rs
      • calcium enters through NMDA
      • calcineurin (PP2B) dephosphorylates I1, leads to disinhibition of PP!, whic activates AMPAR internalization machinery

  • in other words : low Ca2+ - > LTD , high Ca2+ (high frequency stimulation) -> LTP

    • higher frequncy : more NMDA receptor activation

1.2timing

  • if a post-syanptic cell is excited before presynaptic firing, there leads to LDP
  • LTP if presynaptic fire right before the post-synapti stimulation
    • evidence: using BAPTA which flurescent when there's Ca+
      • decrease in flurescence when AP precedes EPSP

1.3Roden hippocampus

  • in CA3 nucelus, the mossy fiber synapses are huge, whereas in CA1 they're small
  • CA1 LTP
    • NMDA-R dependent
  • CA3 LTP
    • NMDA-R independent
    • doesn't require glutamate receptor activation
  • because LTP at CA3 is presynaptic and so is LTP
    • Ca2+ leads to activation of mGluRs on the presynaptic cell
    • this activates AC1
    • decrease in cAMP level leads to reduction of PKA activity
      • this lowers the release probability

2Rabbit eye puffing experiment

  • at the cerebral level (previously been talking in the context of hippocampus)
  • purkinje cells are inhibitory
  • climbing fiber make contact with purkinje cell and can greatly stimulate purkinje cell

  • granule cell extend parallel fibers, touching several purkinje cells but don't sitmilate them as much

  • a puff of air into a rabbit's eye

    • granule cells receive input of sound clue and stimulate
    • climing fiber receives sensory input from eye
    • eventually only sound clue is needed for the rabbit to blind the eye

  • cerebellar LTD

    • depends on mGluR and PKC and result in AMPA internaliation
    • in cerebellum mainly GluA2/GluA3 neurons contain AMPA receptor
    • trafficking are in GluA2 carboxy terminal
    • depolarization and glutamate activaon of mGluRs by parallel fiber leads to activation of PKA in purkinje (NMDA receptor independent)
    • PKC phosphorylates AMPA receptors and leads to internalization by switching binding partners
      • GluA2 was bonud to RIP, a stabilizer first which maintains it on the plasma membrane
      • PKC phosphorylate the SLKV terminus and now PICK binds, which lead to endocytosis

3Endocannabionid

  • retrograde transmitter that binsd to CB1 receptor

  • endogenous cannabinoids cause synaptic depression (several forms)

    • DSI : depolarizzation dependent supression of INHIBITION
    • DSE : depolarization dependent suppression of EXCITATION
    • LTD : long-term depression

  • mechanism

    • released from post-synaptic cell
      • triggered by calcium entry ad mGluR signaling, made from lipid precursor
    • binds to CB1 on presynaptic cell
    • G protein activated
    • G-beta-gamma blocks calcium entry in presynaptic cell
    • CB1 dependent LTD in striatum : a decrease in release probability (p)

4homeostasis

  • neurons try to fire at a target firing rate
    • no activity > cell death
    • too much activity > epilepsy, excitotoxicity

  • homeostasis is demonstrated by

    • adding TTX to block neuron firing and then wash off the drug - > increase in firing
    • adding bicuculine to increase firing and then washing off the drug --> less firing (EPSPs are smaller or less frequent)
    • so neurons are always try to counter balance the drugs

  • synaptic scaling : all neurons in one cell are uniformly up or down regulated

    • AMPA receptor trafficking at all synapse
    • demonstrated by using TTX and bicuculin on cells
    • so unlike LTP/LTD, synaptic scaling isn't specific