Pathologically balanced state as a model for seizures

Pennsylvania State Univ Hershey Med Ctr, Hershey PA

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Abstract

DESCRIPTION (provided by applicant): Seizures are a pathological dynamical state in a neuronal network. Although a tremendous amount of work has been done characterizing physiological aspects of epileptic seizures, there is no dynamical framework linking newly observed single cell interactions to macroscopic network effects. I aim to probe the interplay between single cell characteristics and network dynamics in the formation of seizures. Recently, seizure experiments have revealed previously unknown relationships between synchrony within specific cell types, particular extracellular ionic concentrations, and depolarization block. In order to understand, predict, and treat such aberrant behavior, we must first disentangle the effects each one of these mechanisms have on each other. This investigation will be performed through a compliment of in vitro experiments and simulations of biological network dynamics using models that relate large-scale network activity to single unit cellular and extracellular detail. We intend to refine our models to be able to accurately reproduce experimentally observed phenomena, gain inferences to understand our observations, and make testable predictions regarding initiation, maintenance, and control of seizures.