NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus.
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.
Bekkers
J M
JM
Section of Molecular Neurobiology, Howard Hughes Medical Institute, Yale University Medical School, New Haven, Connecticut 06510.
Stevens
C F
CF
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000502:physiology; D004553:Electric Conductivity; D005971:Glutamates / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D016202:N-Methylaspartate; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D013779:Tetrodotoxin; D016202:N-Methylaspartate