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The Control of Seizure-Like Activity in the Rat Hippocampal Slice

Houman Khosravani^*, Peter L. Carlen^* and Jose L. Perez Velazquez

^* Toronto Western Research Institute, Departments of Paediatrics and Medicine, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada and The Hospital for Sick Children, Brain and Behaviour Programme, University of Toronto, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada

Correspondence: Address reprint requests to J. L. Perez Velazquez, The Hospital for Sick Children, Dept. of Neurology, Room 6535 Hill Wing, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. Tel.: 416-813-7715; Fax: 416-813-7717; E-mail: jlpv{at}sickkids.ca

The sudden and transient hypersynchrony of neuronal firing that characterizes epileptic seizures can be considered as the transitory stabilization of metastable states present within the dynamical repertoire of a neuronal network. Using an in vitro model of recurrent spontaneous seizures in the rat horizontal hippocampal slice preparation, we present an approach to characterize the dynamics of the transition to seizure, and to use this information to control the activity and avoid the occurrence of seizure-like events. The transition from the interictal activity (between seizures) to the seizure-like event is aborted by brief (20–50 s) low-frequency (0.5 Hz) periodic forcing perturbations, applied via an extracellular stimulating electrode to the mossy fibers, the axons of the dentate neurons that synapse onto the CA3 pyramidal cells. This perturbation results in the stabilization of an interictal-like low-frequency firing pattern in the hippocampal slice. The results derived from this work shed light on the dynamics of the transition to seizure and will further the development of algorithms that can be used in automated devices to stop seizure occurrence.

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