CEREBELLAR CIRCUITRY IS ACTIVATED DURING CONVULSIVE EPISODES IN THE TOTTERING (TG TG) MUTANT MOUSE/

Tottering (tg) is an autosomal recessive mutation of the calcium chann el alpha(1A) subunit in the mouse that results in epileptic spike and wave discharges, mild ataxia and paroxysmal episodes of involuntary sp asms of the limbs, trunk and face. These convulsions have been especia lly difficult to characterize because of their unpredictable occurrenc e and lack of electroencephalographic correlates. However, it is, in f act, possible to induce these convulsions, making this facet of the to ttering phenotype amenable to controlled experimentation for the first time. Here, the neuroanatomical basis of the convulsions in tottering mice has been identified using in situ hybridization for c-fos messen ger RNA to chart abnormal neuronal activity. Convulsion-induced c-fos messenger RNA expression was most prominent in the cerebellum of convu lsing tottering mice. Additionally, cerebral cortex and principal cere bellar relay nuclei were also activated during a convulsion. The c-fos activation in the cerebellum temporally preceded expression in cerebr al cortex, suggesting that cerebral cortex is not driving the expressi on of convulsions. These results suggest that the cerebellum, a region not classically associated with paroxysmal events, is important in th e generation and/or maintenance of the intermittent convulsions in tot tering mutant mice. (C) 1998 IBRO. Published by Elsevier Science Ltd.