THE DISTRIBUTION OF SPLICE VARIANTS OF THE NMDAR1 SUBUNIT MESSENGER-RNA IN ADULT-RAT BRAIN

Regional variation in the alternative splice forms of the NMDAR1 subun it mRNA was investigated by in situ hybridization in the adult rat bra in, using radiolabelled splice-specific oligonucleotide probes. Each s plice variant was detected in an individual distribution. The NMDAR1-a and NMDAR1-2 forms were widely and abundantly distributed throughout the brain, except for the inferior colliculus. The NMDAR1-b and NMDAR1 -4 variants were located in similar patterns in fewer areas (e.g. pari etal cortex, hippocampus CA3, thalamus, inferior colliculus, cerebella r granule cells). In contrast, the NMDAR1-1 forms were distributed in a pattern approximately complementary in the forebrain to that of NMDA R1-4 (weakly expressed in thalamus and inferior colliculus). The NMDAR 1-3 variants were not abundant in any structure. Considerable overlap of the in situ hybridization images was noted, so all eight splice com binations are possible in heterogenous distributions. Correlation of t he distribution of NMDAR1 mRNA splice forms with functional analyses o f heteromeric recombinant receptors will be necessary to ascertain if alternative splicing of the NMDAR1 subunit can account for some of the known heterogeneity of endogenous NMDA receptors.