DIFFERENTIAL EXPRESSION OF GLUTAMATE-DECARBOXYLASE MESSENGER-RNA IN CEREBELLAR PURKINJE-CELLS AND DEEP CEREBELLAR NUCLEI OF THE GENETICALLYDYSTONIC RAT

The genetically dystonic rat exhibits a motor syndrome that closely re sembles the human disease, generalized idiopathic dystonia. Although i n humans dystonia is often the result of pathology in the basal gangli a, previous studies have revealed electrophysiological abnormalities a nd alterations in glutamate decarboxylase, the synthetic enzyme for GA BA, in the cerebellum of dystonic rats. In this study, we further char acterized the alterations in cerebellar GABAergic transmission in thes e mutants by examining the expression of the messenger RNA encoding gl utamate decarboxylase (67000 mel. wt) with in situ hybridization histo chemistry at the single cell level in Purkinje cells and neurons of th e deep cerebellar nuclei. Glutamate decarboxylase (67000 mel. wt) mess enger RNA levels were increased in the Purkinje cells and decreased in the deep cerebellar nuclei of dystonic rats compared to control litte rmates, suggesting opposite changes in GABAergic transmission in Purki nje cells and in their target neurons in the deep cerebellar nuclei. I n contrast, levels of glutamate decarboxylase (67000 mel. wt) messenge r RNA in the pallidum, and of enkephalin messenger RNA in the striatum , were unaffected in dystonic rats. The data indicate that both the Pu rkinje cells and GABAergic neurons of the deep cerebellar nuclei are t he site of significant functional abnormality in the dystonic rat. (C) 1997 IBRO. Published by Elsevier Science Ltd.