ALTERED INTRACELLULAR-LOCALIZATION OF THE GLUTAMATE-RECEPTOR CHANNEL DELTA-2 SUBUNIT IN WEAVER AND REELER PURKINJE-CELLS

The glutamate receptor (GluR) channel delta 2 subunit is expressed abu ndantly and specifically in cerebellar Purkinje cells. Our previous st udy demonstrated that the GluR delta 2 mRNA is expressed as early as e mbryonic day 15 prior to Purkinje cell synaptogenesis, and its protein product accumulates in dendritic spines during normal Purkinje cell m aturation. In this study, we examined expression and distribution of t he GluR delta 2 in the weaver and reeler mutant cerebelli, which show abnormal cytoarchitecture and neural circuitry. In situ hybridization analysis showed that GluR delta 2 mRNA was expressed in entire Purkinj e cells in both mutant mice. Immunohistochemical analysis revealed tha t intracellular localization of GluR delta 2 was altered in some regio n of mutant cerebelli. In the cortical surface where Purkinje cells fo rm synapses with parallel fibers, GluR delta 2-immunoreactivity was re stricted to dendritic spines of Purkinje cells as observed in normal m ice. In contrast, in the subcortical region where granule cells and pa rallel fibers are absent, the immunoreactivity was found widely in Pur kinje dendrites. Thus, the GluR gamma 2 protein did not accumulate to the dendritic spines of Purkinje cells lacking synaptic contact with p arallel fibers. These results suggest that the expression of both GluR delta 2 mRNA and protein is independent of abnormalities in the mutan t cerebelli, but relocalization of the GluR delta 2 protein might depe nd on the formation of synapses between Purkinje cells and parallel fi bers.