| Research Abstract |
We investigated functional roles of ion channels in generating basic brain rhythmic activity, through analyses of synaptic transmission and neuronal activity of spontaneously mutated or knockout mice. Mutations of the ion channels directly or indirectly affect the neuronal circuits.
The N-type calcium channel knockout mice were produced. Because the N-type channel was supposed to be the main calcium channel, we expected neurological deficits. But the knockout mice were apparently normal, without visible neurological deficits. They were fertile. Detailed studies, however, revealed that the N-type knockout mice had disturbed circulatory homeostasis which is regulated by the sympathetic nervous system. They may serve as a good model for studying spontaneous hypertension.
We investigated the mechanism how the mutations of the P/Q-type calcium channel lead to neurological symptoms (cerebellar ataxia, seizure of absence type) in mutant mice (tottering, leaner, and rolling). In mutant cerebellar ataxic mice, synaptic transmission from parallel fibers to Purkinje cells was impaired, and the degree of the impairment correlated with the symptom of ataxia. However, the synaptic transmission from climbing fibers to Purkinje cells was preserved, or even enhanced. These observations suggest that disturbed calcium metabolism leads to various changes in synaptic connections, and underscores the important role of calcium in the development and maintenance of neural activity.
We investigated thalamo-cortical connection in tottering mice which show absence-type seizure. We found that the inhibitory input was disproportionally reduced. This input may function as feed forward inhibition system to prevent the cerebral cortex from hyperactivation.
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