NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus

Nature. 1989 Sep 21;341(6239):230-3. doi: 10.1038/341230a0.


A CENTRAL assumption about long-term potentiation in the hippocampus is that the two classes of glutamate-receptor ion channel, the N-methyl-D-aspartate (NMDA) and the kainate/quisqualate (non-NMDA) subtypes, are co-localized at individual excitatory synapses. This assumption is important because of the perceived interplay between NMDA and non-NMDA receptors in the induction and expression of long-term potentiation: the NMDA class, by virtue of its voltage-dependent channel block by magnesium and calcium permeability, provides the trigger for the induction of long-term potentiation, whereas the actual enhancement of synaptic efficacy is thought to be provided by the non-NMDA class. If both receptor subtypes are present at the one synapse, such cross-modulation could occur rapidly and locally through diffusible factors. By measuring miniature synaptic currents in cultured hippocampal neurons we show that the majority (approximately 70%) of the excitatory synapses on a postsynaptic cell possess both kinds of receptor, although to different extents. Of the remaining excitatory synapses, approximately 20% contain only the non-NMDA subtype and the rest possess only NMDA receptors. This finding provides direct evidence for co-localization of glutamate-receptor subtypes at individual synapses, and also points to the possibility that long-term potentiation might be differentially expressed at each synapse according to the mix of receptor subtypes at that synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / physiology
  • Electric Conductivity
  • Glutamates / physiology
  • Hippocampus / physiology*
  • N-Methylaspartate
  • Neurotransmitter Agents / physiology
  • Rats
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / physiology*
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Transmission
  • Tetrodotoxin / pharmacology


  • Glutamates
  • Neurotransmitter Agents
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Aspartic Acid
  • Tetrodotoxin
  • N-Methylaspartate