DIFFERENTIAL EXPRESSION OF AMPA RECEPTOR SUBUNITS IN NOS-POSITIVE NEURONS OF CORTEX, STRIATUM, AND HIPPOCAMPUS

AMPA receptor (AMPAR) subunits expression was studied in nitric oxide synthase (NOS)-positive neurons of the adult rat cortex, striatum, and hippocampus, by a double-labeling approach, combining nonradioactive in situ hybridization and immunocytochemistry. The majority of cortica l and hippocampal NOS-immunopositive neurons were characterized by a p redominant expression of GluR-A and -D mRNA and low or undetectable ex pression of GluR-B and -C mRNA, In the striatum, the expression profil e of AMPAR subunits in NOS-positive neurons differed from that in the other two regions, This is reflected in the overall low expression of all AMPA receptor subunits and the paucity of GluR-D subunit expressio n that contrasts with the high expression bf this subunit in NOS-posit ive cells in the hippocampus. Double-labeling experiments revealed a s ubstantial correspondence between mRNA and protein levels of AMPAR sub units, Further evidence for the regional diversity of NOS-positive neu rons is derived from the expression analysis of glutamate decarboxylas e (GAD)-55 and -67 mRNAs, NOS-positive neurons expressed high levels o f GAD-65, but not -67 in the cortex, high levels of both forms in the hippocampus, and low or undetectable levels of both mRNAs in the stria tum, Despite of these differences, NOS-positive neurons share the comm on feature of low GluR-B subunit expression, suggesting the presence o f AMPAR channels with high Ca2+ permeability, regardless of the region al location, The relative resistance of NOS-positive interneurons in n eurodegenerative diseases suggests that glutamate receptor-mediated Ca 2+ influx alone does not suffice to explain neuronal vulnerability, an d additional factors have thus to be considered.