Organization, control and function of extrasynaptic NMDA receptors

Philos Trans R Soc Lond B Biol Sci. 2014 Oct 19;369(1654):20130601. doi: 10.1098/rstb.2013.0601.

Abstract

N-methyl D-aspartate receptors (NMDARs) exist in different forms owing to multiple combinations of subunits that can assemble into a functional receptor. In addition, they are located not only at synapses but also at extrasynaptic sites. There has been intense speculation over the past decade about whether specific NMDAR subtypes and/or locations are responsible for inducing synaptic plasticity and excitotoxicity. Here, we review the latest findings on the organization, subunit composition and endogenous control of NMDARs at extrasynaptic sites and consider their putative functions. Because astrocytes are capable of controlling NMDARs through the release of gliotransmitters, we also discuss the role of the glial environment in regulating the activity of these receptors.

Keywords: NMDA receptors; d-serine; excitotoxicity; glycine; plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • Humans
  • Long-Term Potentiation / physiology*
  • Long-Term Synaptic Depression / physiology*
  • Neurotoxins / metabolism*
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Signal Transduction / physiology*

Substances

  • NR2B NMDA receptor
  • Neurotoxins
  • Receptors, N-Methyl-D-Aspartate