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2008年09月16日

Biophysical insights on the neurobiology of the 'Falling Sickness'

日 時 2008年09月16日(火) 17:00 より 19:00 まで
講演者 Professor S.K. Sikdar
講演者所属 Molecular Biophysics Unit, Indian Institute of Science, India
お問い合わせ先 鍋倉淳一(生体恒常機能発達機構研究部門 内線 7851)
要旨

Falling sickness is an old term for epilepsy. Epilepsy is characterized by highly synchronous activity of neurons. One of our research interests is directed at understanding this neurological disorder at the level of ion channels, single neurons and neuronal network, primarily using electrophysiological approaches.

At the single neuron level, epileptic activity manifests as 'paroxysmal depolarization shifts' in the membrane potential that last for seconds to minutes. Our studies on voltage gated sodium channels that are important in action potential initiation, indicate pseudo-periodic oscillation in the channel properties that is dependent on the duration of membrane depolarization. The results suggest alteration of ion channel properties following epileptic episodes and the probable role of these channels in the genesis of epileptic activity in turn. This was confirmed using whole-cell and single-channel patch-clamp recordings.

Epileptic seizures are associated with neuronal death and this follows high levels of intracellular calcium. In experiments designed to understand the cellular changes in epileptic neurons, we have observed changes in the calcium dynamics and calcium diffusion co-efficients in the dendrites of autaptic hippocampal neurons that were made epileptic with kynurenate treatment. The `subiculum`,is at the transition zone between the hippocampus and the entrorhinal cortex and has been implicated in epileptiform activity. Combined electrophysioligical and Ca imaging experiments revealed distance dependent changes in the Ca2+ decay kinetics in the apical dendrites of subicular pyramidal neurons that are made epileptic.

In order to understand changes in neuronal network activity during epileptic seizures we have conducted studies on hippocampal neurons cultured on planar multi-electrode arrays containing 64 electrodes. Results suggest changes in neuronal network burst properties and neuronal network topology analyzed using Graph Theory approaches, in neuronal network cultures that are made epileptic.