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Slow excitatory synaptic currents generated by AMPA receptors.

Niccolò P Pampaloni1,2,3, Andrew J R Plested1,2,3

  • 1Institute of Biology, Cellular Biophysics, Humboldt Universität zu Berlin, Berlin, Germany.

The Journal of Physiology
|September 29, 2021
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Summary

AMPA receptors, traditionally fast, can exhibit slow, sustained currents via auxiliary subunits. This

Keywords:
auxiliary subunitsglutamatekineticsshort-term plasticitysynaptic diversity

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Transmission

Background:

  • AMPA-type glutamate receptors are typically fast-acting neurotransmitter receptors.
  • Conventional understanding posits rapid activation and deactivation due to low glutamate affinity and desensitization.
  • These properties traditionally limit AMPA receptor function in space and time.

Purpose of the Study:

  • To review evidence for slow AMPA receptor activation modes.
  • To challenge the notion that slow AMPA currents are limited to non-native expression systems.
  • To explore the implications of slow AMPA currents for synaptic transmission and neural computation.

Main Methods:

  • Literature review of studies on AMPA receptor kinetics and function.
  • Analysis of evidence for slow AMPA currents in native nervous systems.
  • Examination of the role of auxiliary subunits in modulating AMPA receptor activity.

Main Results:

  • Accumulating evidence demonstrates slow, indefatigable AMPA receptor responses.
  • Auxiliary subunits can induce a 'superactive' mode with high open probability and sustained currents.
  • Slow AMPA currents, characterized by lack of desensitization and prolonged decay, are widespread in the nervous system.
  • These slow currents contribute to short-term potentiation and operate within cognitive time scales (e.g., theta rhythms).

Conclusions:

  • Slow AMPA currents are not limited to heterologous expression but are prevalent in native synapses.
  • The 'superactive' mode of AMPA receptors has significant implications for excitatory synaptic transmission.
  • Slow AMPA currents provide a postsynaptic mechanism for short-term plasticity and neural computation, particularly in the hippocampus.