Localization of alternatively spliced NMDAR1 glutamate receptor isoforms in rat striatal neurons

Alternative splicing of the mRNA encoding the N-methyl-D-aspartate (NMDA) r eceptor subunit NR1 changes the structural, physiologic, and pharmacologic properties of the resultant NMDA receptors. We used dual label immunocytoch emistry and confocal microscopy to localize the four alternatively spliced segments of the NR1 subunit (N1, C1, C2, and C2') in rat striatal neurons. Striatofugal projection neurons and four populations of interneurons were s tudied. Projection neurons, which were identified by immunolabeling for cal bindin and by retrograde tracing from the globus pallidus and the substanti a nigra, were the only striatal neurons containing C1 segment immunoreactiv ity. Projection neurons were also C2 segment immunopositive, as were all ot her neuronal populations studied. Projection neurons were C2' segment immun onegative. In contrast, each of the interneuron types were labeled by the a ntibody to the C2' segment: nitric oxide synthase interneurons were labeled intensely, calretinin and parvalbumin neurons were labeled moderately stro ngly, and cholinergic neurons were also labeled but less strongly than the other types of interneurons. Parvalbumin interneurons showed distinct N1 se gment immunolabeling, which was not found in other types of striatal neuron s. Our results suggest that all striatal neurons studied synthesize NR1 sub unit proteins, but the isoforms of the protein present in projection neuron s and the several types of interneurons are distinct. This differential exp ression of NR1 isoforms may affect both neuronal function and selective vul nerability of neurons to injury. (C) 1999 Wiley-Liss, Inc.