Presynaptic NMDA receptors in the neocortex are both auto- and heteroreceptors

We used electron microscopic immunocytochemistry with antibodies against NR1 and NR2A and B subunits to study the distribution of N-methyl-D-aspartate (NMDA) receptors in presynaptic axon terminals in the rat cerebral cortex. In all sections examined, NR1 and NR2A/B immunoreactivities were observed in axon terminals: NR1- and NR2A/B-positive axon terminals made both symmetrical and asymmetrical synapses on unlabelled dendritic profiles. Combined pre- and postembedding studies showed that all NR1 and NR2A/B-positive axon terminals making symmetrical synapses were gamma-aminobutyric acid (GABA)-positive. These observations show that both auto- and hetero- NMDA receptors do exist in the cerebral cortex, and indicate that part of the effects of NMDA receptor activation might be determined by modulating glutamate and GABA release.