Cerebellar circuitry is activated during convulsive episodes in the tottering (tg/tg) mutant mouse.
Tottering (tg) is an autosomal recessive mutation of the calcium channel alpha1A subunit in the mouse that results in epileptic spike and wave discharges, mild ataxia and paroxysmal episodes of involuntary spasms of the limbs, trunk and face. These convulsions have been especially difficult to characterize because of their unpredictable occurrence and lack of electroencephalographic correlates. However, it is, in fact, possible to induce these convulsions, making this facet of the tottering 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 messenger RNA to chart abnormal neuronal activity. Convulsion-induced c-fos messenger RNA expression was most prominent in the cerebellum of convulsing tottering mice. Additionally, cerebral cortex and principal cerebellar relay nuclei were also activated during a convulsion. The c-fos activation in the cerebellum temporally preceded expression in cerebral cortex, suggesting that cerebral cortex is not driving the expression of convulsions. These results suggest that the cerebellum, a region not classically associated with paroxysmal events, is important in the generation and/or maintenance of the intermittent convulsions in tottering mutant mice.
Campbell
D B
DB
Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Hess
E J
EJ
D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D017781:Genes, Immediate-Early / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology; D013997:Time Factors
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger