NMDA RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION BY PROJECTION NEURONS AND INTERNEURONS IN RAT STRIATUM

N-Methyl-D-aspartate (NMDA) receptors are enriched in the neostriatum and are thought to mediate several actions of glutamate including neur onal excitability, long-term synaptic plasticity, and excitotoxic inju ry, NMDA receptors are assembled from several subunits (NMDAR1, NMDAR2 A-D) encoded by five genes; alternative splicing gives rise to eight i soforms of subunit NMDAR1, We studied the expression of NMDA receptor subunits in neurochemically identified striatal neurons of adult rats by in situ hybridization histochemistry using a double-labeling techni que, Enkephalin-positive projection neurons, somatostatin-positive int erneurons, and cholinergic interneurons each have distinct NMDA recept or subunit phenotypes, Both populations of striatal interneurons exami ned express lower levels of NMDAR1 and NMDAR2B subunit mRNA than enkep halin-positive neurons, The three striatal cell populations differ als o in the presence of markers for alternatively spliced regions of NMDA R1, suggesting that interneurons preferentially express NMDAR1 splice forms lacking one (cholinergic neurons) or both (somatostatin-positive neurons) alternatively spliced carboxy-terminal regions, In addition, somatostatin- and cholinergic-, but not enkephalin-positive neurons e xpress NMDAR2D mRNA, Thus, these striatal cell populations express dif ferent NMDAR-subunit mRNA phenotypes and therefore are likely to displ ay NMDA channels with distinct pharmacological and physiological prope rties, Differences in NMDA receptor expression may contribute to the r elative resistance of striatal interneurons to the neurotoxic effect o f NMDA receptor agonists.