Neuronal and glial localization of NMDA receptors in the cerebral cortex

The crucial role of glutamate receptors of the N-methyl-D-aspartate (NMDA) type in many fundamental cortical functions has been firmly established, as has its involvement in several neuropsychiatric diseases, but until recently, very little was known of the anatomical localization of NMDA receptors in the cerebral cortex of mammals. The recent application of molecular biological techniques to the study of NMDA receptors has allowed the production of specific tools, the use of which has much increased our understanding of the localization of NMDA receptors in the cerebral cortex. In particular, immunocytochemical studies on the distribution of cortical NMDA receptors have: 1. Demonstrated the preferential localization of NMDA receptors in dendritic spines, in line with previous work; 2. Disclosed a thus far unknown fraction of presynaptic NMDA receptors on both excitatory and inhibitory axon terminals: and 3. Shown that cortical astrocytes express NMDA receptors. These studies indicate that the effects of cortical NMDA receptor activation are not caused exclusively by the opening of NMDA channels on neuronal postsynaptic membranes, as previously assumed, and that the activation of presynaptic and glial NMDA receptors can contribute significantly to these effects.