MECHANISMS OF FOCAL AND GENERALIZED SPIKE WAVE SEIZURES

Salk Institute For Biological Studies, La Jolla CA

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Abstract

DESCRIPTION: (Adapted from the Investigator's Abstract): The intrinsic cellular, synaptic and network mechanisms underlying cortically-initiated electrographical seizures will be explored with electrophysiological experiments in vivo and in computational modeling I studies. The electrographical seizures observed in cat neocortex resemble partial and generalized epileptic | seizures consisting of spike-wave (SW) or polyspike-wave (PSW) complexes at 1.5 about Hz and fast runs at 10 15 Hz. We will study (a) specific cellular and network mechanisms responsible for the onset, maintenance and I termination of the paroxysmal seizures; (b) the specific and common properties of different types of | electrographical seizures; (c) the conditions responsible for transforming spatially localized paroxysmal activity into generalized seizure. Compartmental models of excitatory and inhibitory neocortical neurons and their interactions will be used to examine specific hypotheses for the mechanisms underlying multiple intracortical processes preceding, accompanying and following electrographic seizures and to generate predictions that can be tested experimentally. These models may also be useful for preliminary screening of antiepileptic drags. The methods that will be used in these studies include (a) in vivo multisided intracellular and l field potential recordings from anesthetized and behaving animals to probe specific intracellular and synaptic changes during seizure; (b) recently developed independent component analysis (ICA) applied to the I electrophysiological data to study spatio-temporal properties of paroxysmal activity; (c) computational modeling based on detailed description of the intrinsic properties of individual neurons and their synaptic interconnections. The modeling techniques are aimed at understanding paroxysmal seizure mechanisms by simultaneous and independent observations of all contributing factors, some of which are difficult to study experimentally. Electrophysiological recordings and preliminary analysis of the experimental data will beconducted in Laval University (Canada) and detailed computational analysis based on ICA methods and modeling techniques will be conducted in the Salk Institute (USA). These studies may lead to new treatments for epilepsy based on comparisons between models for the normal and diseased states of the cortex.