EVIDENCE FOR PRESYNAPTIC N-METHYL-D-ASPARTATE AUTORECEPTORS IN THE SPINAL-CORD DORSAL HORN

The N-methyl-D-aspartate (NMDA) receptor has been implicated in a vari ety of systems that undergo plastic changes in the central nervous sys tem. We used electron microscopic immunocytochemistry with an antibody directed against an alternatively spliced exon near the C terminus of NMDAR1, the essential functional subunit of the NMDA receptor, to stu dy the distribution of the NMDA receptor in the spinal cord and CA1 re gion of the hippocampus, two regions where NMDA-mediated long-term pla sticity has been demonstrated, In CA1, we found that the NMDA receptor is exclusively expressed on postsynaptic structures. By contrast, in the spinal cord we found that in about one-third of labeled synapses, the receptor is located in the presynaptic terminal, immediately adjac ent to the vesicle release site at the active zone. Using combined pos tembedding immunocytochemistry, we also showed that >70% of the NMDA r eceptor immunoreactive terminals are glutamate positive, which suggest s that the presynaptic NMDA receptor is an autoreceptor. Nerve ligatio n studies demonstrated that the receptor is transported in dorsal root s and sciatic nerve to the spinal cord and periphery, respectively. Th ese data indicate that an NMDA autoreceptor is located in terminals of primary afferent fibers, where it could facilitate the transmission o f inputs to the spinal cord by increasing the release of neurotransmit ter from the primary afferent terminal.