Investigation of the role of the cerebellum in the myoclonic-like movement disorder exhibited by tottering mice.
Recently it has been discovered that defects in neuronal ion channels can result in seizure disorders. The tottering mouse is a genetic animal model carrying a mutation in the alpha1A calcium channel subunit that causes these mice to exhibit generalized petit mal-like epilepsy, cerebellar ataxia, and an intermittent movement disorder that has some characteristics similar to myoclonus or myoclonic epilepsy. We postulate that abnormal cerebellar Purkinje cell output to the deep cerebellar nuclei results in the intermittent movement disorder observed in these mice. The frequency and duration of seizure activity were measured in tottering mice before and 2 weeks after surgical or chemical lesioning of the cerebellum. Surgical lesions in the anterior cerebellar vermis of tottering mice produced significant reductions in seizure duration and frequency. Surgical lesioning of the posterior cerebellar vermis had no significant effect. Chemical lesions of the same cerebellar regions, using a locally applied neurotoxin, NMD-L-A, appear to produce effects similar to the surgical lesions. These data indicate that anterior vermal cerebellar output is important for production of the seizures associated with the intermittent movement disorder observed in tottering mice.
Abbott
L C
LC
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station 77843-4458, USA.
Bump
M
M
Brandl
A
A
De Laune
S
S
D000818:Animals; D001931:Brain Mapping; D015220:Calcium Channels / Q000502:physiology; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002525:Cerebellar Cortex / Q000503:physiopathology; D002529:Cerebellar Nuclei / Q000503:physiopathology; D002531:Cerebellum / Q000503:physiopathology*; D004831:Epilepsies, Myoclonic / Q000503:physiopathology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009207:Myoclonus / Q000503:physiopathology*; D009638:Norepinephrine / Q000502:physiology; D011689:Purkinje Cells / Q000502:physiology
D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D009638:Norepinephrine