Long Term Potentiation in Vertebrates

Long-Term Potentiation (LTP)
1. one+ axons connected to dendrite bombard it with rapid series of stimuli
  1. burst of intense stimulation leaves some of the synapses potentiated for minutes, days or weeks
2. Specificity
  1. if some of synapses onto cell have been highly active and others haven't, only active ones become strengthened
3. cooperativity
  1. nearly simultaneous stimulation by two+ axons produces LTP more strongly than repeated stimulation by just one axon
4. Associativity
  1. pairing weak input with strong input enhances later response to weak input.
    1. LTP matches what we would expect of Hebbian synapses
      1. Synapse that was almost completely inactive before LTP becomes effective afterward
        Kerchner & Nicoll (2008)
5. Long-term depression (LTD)
  1. prolonged decrease in response at a synapse, occurs for axons that have been less active than others
    1. compensatory process
    2. as one synapse strengthens, another weakens
      1. Royer & Pare (2003)
AMPA and NMDA Synapses
1. in few cases, LTP depends on GABA synapses
  1. in most it depends on changes in glutamate synapses
    1. brain has several receptors for glutamate
      1. NT identify diff dopamine receptors by number and diff GABA receptors by letter
      2. for glutamate, named different receptors after certain drugs that stimulate them
2. AMPA receptor excited by NT glutamate but can respond to drug called AMPA
3. NMDA receptor also ordinarily excited only by glutamate but can respond to drug called NMDA
4. both are ionotropic receptors
  1. when they are stimulated they open a channel to let ions enter the postsynaptic cell
  2. AMPS receptor typical ion tropic receptor opens sodium channels
  3. NMDA receptor is diff: response to transmitter glutamate depends on degree of polarisation across the membrane
5. when glutamate attaches to NMDA receptor while membrane is at resting potential, ion channel is blocked by magnesium ions
  1. NMDA channel opens only if magnesium leaves and surest way to detach magnesium is to depolarise membrane, decreasing negative charge that attracts it
Presynaptic Changes
1. LTP depends on changes in the presynaptic neurone instead or in addition
2. Extensive stimulation of postsynaptic cell causes it to release a retrograde transmitter that travels back to presynaptic cell to modify it
  1. in many cases, retrograde transmitter is nitric oxide
  2. As a result, presynaptic neurone decreases its threshold for producing at ion potentials
    1. increases release of NT
      1. expands its axon
        releases its transmitter from additional sites along its axon
3. LTP reflects increased activity by the presynaptic neurone as well as increase responsiveness by the post-synaptic neurone
Consolidation Revisted
1. LTP in hippo is important for certain types of learning
  1. as time passes and learning proceeds, memory become less dependent on hippo and more on cerebral cortex
    1. gradual over varying periods of time
  2. fMRI showed after people learned some associations they showed more activity in hippo after 15 min
    1. and more in cerebral cortes after 24 hours
      1. Takashima et al (2009)
2. we demonstrate a shift to cerebral cortex both over period of one day and many years

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Long Term Potentiation in Vertebrates

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