Expression of NMDA receptor subunit mRNAs in neurochemically identified projection and interneurons in the human striatum

N-methyl-D-aspartate (NMDA) receptors are composed of subunits from two fam ilies: NR1 and NR2. We used a dual-label in situ hybridization technique to assess the levels of NR1 and NR2A-D messenger ribonucleic acid (mRNA) expr essed in projection neurons and interneurons of the human striatum. The neu ronal populations were identified with digoxigenin-tagged complementary RNA probes for preproenkephalin (ENK) and substance P (SP) targeted to striata l projection neurons, and somatostatin (SOM), glutamic acid decarboxylase 6 7 kD (GAD(67)), and choline acetyltransferase (ChAT) targeted to striatal i nterneurons. Intense NR1 signals were found over all striatal neurons. NR2A signals were high over GAD(67)-positive neurons and intermediate over SP-p ositive neurons. ENK-positive neurons displayed low NR2A signals, whereas C hAT- and SOM-positive neurons were unlabeled. NR2B signals were intense ove r all neuronal populations in striatum. Signals for NR2C and NR2D were weak . Only ChAT-positive neurons displayed moderate signals, whereas all other interneurons and projection neurons were unlabeled. Moderate amounts of NR2 D signal were detected over SOM- and ChAT-positive neurons; GAD(67)- and SP -positive striatal neurons displayed low and ENK-positive neurons displayed no NR2D hybridization signal. These data suggest that all human striatal n eurons have NMDA receptors, but different populations have different subuni t compositions that may affect function as well as selective vulnerability. J. Comp. Neurol. 419:407-421, 2000. (C) 2000 Wiley-Liss, Inc.