REGIONAL AND DEVELOPMENTAL HETEROGENEITY IN SPLICING OF THE RAT-BRAINNMDAR1 MESSENGER-RNA

Developmental and regional alternative splicing of the NMDAR1 subunit gene transcript was examined by in site hybridization in the developin g and adult rat brain. NMDAR1 mRNA, barely detectable at embryonic day 14, increased gradually during development until the third postnatal week, after which it declined slightly to adult levels, when it was de tected in every examined neuronal type. Each splice form of the primar y NMDAR1 gene transcript was found to follow a parallel profile of abu ndance in the brain, but marked regional differences were observed in splicing at both 5' and 3' sequences. The individual regional distribu tions of splice forms appeared to be established around birth, with li ttle change thereafter, except in the overall abundance. The NMDAR1-a and NMDAR1-2 splice forms occurred extensively and approximately homog eneously throughout brain gray matter. The NMDAR1-b variant was found primarily in the sensorimotor cortex, neonatal lateral caudate, thalam us, hippocampal CA3 field, and cerebellar granule cells, but was absen t from adult caudate. The NMDAR1-1 and -4 splice forms were detected i n almost complementary patterns; the former was concentrated in more r ostral structures such as cortex, caudate, and hippocampus, while the latter was principally in more caudal regions such as thalamus, collic uli, and cerebellum. These two splice forms accounted for a greater pr oportion of the adult NMDAR1 mRNA than that of the neonate. The NMDAR1 -3 mRNA variant was scarce, being detected only at very low levels in postnatal cortex and hippocampus. The different splice forms may gener ate regional differences in NMDA receptor properties during developmen t and in the adult CNS.