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 cortical and hippocampal NOS-immunopositive neurons were characterized by a predominant expression of GluR-A and -D mRNA and low or undetectable expression of GluR- B and -C mRNA. In the striatum, the expression profile 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 expression that contrasts with the high expression of this subunit in NOS-positive cells in the hippocampus. Double-labeling experiments revealed a substantial correspondence between mRNA and protein levels of AMPAR subunits. Further evidence for the regional diversity of NOS- positive neurons is derived from the expression analysis of glutamate decarboxylase (GAD)-65 and -67 mRNAs. NOS-positive neurons expressed high levels of 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 striatum. Despite of these differences, NOS-positive neurons share the common feature of low GluR-B subunit expression, suggesting the presence of AMPAR channels with high Ca²⁺ permeability, regardless of the regional location. The relative resistance of NOS-positive interneurons in neurodegenerative diseases suggests that glutamate receptor-mediated Ca²⁺ influx alone does not suffice to explain neuronal vulnerability, and additional factors have thus to be considered.