Neuronal and glial localization of NR1 and NR2A/B subunits of the NMDA receptor in the human cerebral cortex

N-Methyl-D-aspartate (NMDA) receptors play a critical role in many cortical functions and are implicated in several neuropsychiatric diseases. In this study, the cellular expression of the NMDAR1 (NR1) acid NMDAR2A and B (NR2 A and B) subunits was investigated in the human cerebral cortex by immunocy tochemistry with antibodies that recognize the NR1 or the NR2A and B subuni ts of the NMDA receptor. In frontal (areas 10 and 46) and temporal (area 21 ) association cortices and the cingulofrontal transition cortex (area 32), hint and NR2A/B immunoreactivity (ir) were similar and were localized to nu merous neurons in all cortical layers. NR1- and NR2A/B-positive neurons wer e mostly pyramidal cells, but some nonpyramidal neurons were also labeled. Electron-microscopic observations showed that NR1 and NR2A/B ir were simila r. In all cases, labeling of dendrites and dendritic spines was intense. In addition, both NR1 and NR2A/B were consistently found in the axoplasm of s ome axon terminals and in distal astrocytic processes. This investigation r evealed that numerous NMDA receptors are localized to dendritic spines, and that they are also localized to axon terminals and astrocytic processes. T hese findings suggest that the effects of cortical NMDA activation in the h uman cortex do not depend exclusively on the opening of NMDA channels locat ed at postsynaptic sites, and that the localization of NMDA receptors is si milar in a variety of mammalian species.