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Expression mechanisms underlying long-term potentiation: a postsynaptic view.

Roger A Nicoll1

  • 1Departments of Cellular and Molecular Pharmacology and Physiology, University of California San Francisco, San Francisco, CA 94143, USA. nicoll@cmp.ucsf.edu

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|May 13, 2003
PubMed
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Long-term potentiation (LTP) involves changes in synaptic strength. Research suggests N-methyl-D-aspartate (NMDA) receptor-dependent LTP primarily occurs postsynaptically, not presynaptically.

Area of Science:

  • Neuroscience
  • Synaptic Plasticity

Background:

  • Long-term potentiation (LTP) is a key mechanism for learning and memory.
  • Determining whether LTP expression is presynaptic or postsynaptic is crucial for understanding synaptic plasticity.

Purpose of the Study:

  • To review experimental evidence regarding the location of N-methyl-D-aspartate (NMDA) receptor-dependent LTP expression.
  • To evaluate the contributions of presynaptic and postsynaptic mechanisms in LTP.

Main Methods:

  • Analysis of experimental data on glutamate overflow and synaptic failure rates.
  • Review of studies on astrocytic glutamate transporter currents.
  • Examination of findings related to silent synapses and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function.

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Main Results:

  • Conflicting evidence exists regarding presynaptic mechanisms, with some studies showing increased glutamate overflow and decreased failure rates, while others detect no change in glutamate release.
  • The discovery of silent synapses switching on AMPA receptor function offers a postsynaptic explanation for decreased failure rates.
  • Evidence increasingly favors postsynaptic mechanisms for LTP expression.

Conclusions:

  • NMDA receptor activation leads to rapid AMPA receptor recruitment.
  • Covalent modification of synaptic AMPA receptors is another postsynaptic mechanism involved in LTP.
  • The preponderance of evidence supports a postsynaptic locus for NMDA receptor-dependent LTP expression.