DIFFERENTIAL EXPRESSION AND COASSEMBLY OF NMDA-ZETA-1-SUBUNIT AND NMDA-EPSILON-SUBUNIT IN THE MOUSE CEREBELLUM DURING POSTNATAL-DEVELOPMENT

THE differential distribution of NMDA receptor subunit mRNAs in the de veloping mammalian cerebellum has been previously described. In this s tudy, we investigated the temporal expression of NMDA receptor protein s in the postnatal murine cerebellum using antibodies specific for the NMDA zeta 1 and NMDA epsilon subunits. Our results showed a gradual i ncrease during the first three weeks of life in the relative amount of NMDA zeta 1 and NMDA epsilon 1 proteins. In contrast, NMDA epsilon 2 increased transiently during this period, reaching a maximum around po stnatal day 9 and decreasing thereafter to nearly undetectable levels by the end of the third Reek of life. The level of NMDA epsilon 3 incr eased dramatically between postnatal days 9 and 15 and thereafter rema ined constant. Immunoprecipitation of native proteins revealed that a large fraction of NMDA epsilon 2 was associated with NMDA zeta 1 and e psilon 1. At later developmental stages, NMDA epsilon 3 was predominan tly assembled with NMDA zeta 1 but not with NMDA epsilon 1 or NMDA eps ilon 2. These results demonstrate that NMDA receptor subtypes, formed by the assembly of different NMDA epsilon subunits with NMDA zeta 1, a re sequentially expressed in the developing mouse cerebellum. The time course of their expression suggest, that these NMDA receptor subtypes may contribute to specific aspects of granule cell differentiation in the cerebellum.