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

JM Bekkers, CF Stevens - Nature, 1989 - nature.com
Nature, 1989nature.com
A CENTRAL assumption about long-term potentiation in the hip-pocampus 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
synapses1, 2. This assumption is important because of the perceived interplay between
NMDA and non-NMDA receptors in the induc-tion and expression of long-term potentiation:
the NMDA class, by virtue of its voltage-dependent channel block by magnesium3, 4 and …
Abstract
A CENTRAL assumption about long-term potentiation in the hip-pocampus 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 synapses1,2. This assumption is important because of the perceived interplay between NMDA and non-NMDA receptors in the induc-tion and expression of long-term potentiation: the NMDA class, by virtue of its voltage-dependent channel block by magnesium3,4 and calcium permeability5,6, 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 class7,9. 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 (∼70%) of the excitatory synapses on a postsynaptic cell possess both kinds of receptor, although to different extents. Of the remaining excita-tory synapses, ∼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.
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