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 abundantly and specifically in cerebellar Purkinje cells. Our previous study demonstrated that the GluR is expressed as early as embryonic day 15 prior to Purkinje cell synaptogenesis, and its protein product accumulates in dendritic spines during normal Purkinje cell maturation. In this study, we examined expression and distribution of the 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 Purkinje cells in both mutant mice. Immunohistochemical analysis revealed that intracellular localization of GluR delta 2 was altered in some region of mutant cerebelli. In the cortical surface where Purkinje cells from synapses with parallel fibers, GluR delta 2-immunoreactivity was restricted to dendritic spines of Purkinje cells as observed in normal mice. In contrast, in the subcortical region where granule cells and parallel fibers are absent, the immunoreactivity was found widely in Purkinje dendrites. Thus, the GluR delta 2 protein did not accumulate to the dendritic spines of Purkinje cells lacking synaptic contact with parallel fibers. These results suggest that the expression of both GluR delta 2 mRNA and protein is independent of abnormalities in the mutant cerebelli, but relocalization of the GluR delta 2 protein might depend on the formation of synapses between Purkinje cells and parallel fibers.