Molecular mechanisms of epilepsy

Abstract

Decades of experimental work have established an imbalance of excitation and inhibition as the leading mechanism of the transition from normal brain function to seizure. In epilepsy, these transitions are rare and abrupt. Transition processes incorporating positive feedback, such as activity-dependent disinhibition, could provide these uncommon timing features. A rapidly expanding array of genetic etiologies will help delineate the molecular mechanism(s). This delineation will entail quite a bit of cell biology. The genes discovered so far are more remarkable for their diversity than their similarities.

Figures

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Episodic surges in network activity may rarely cross a “seizure threshold” of activity level at which positive feedback mechanisms such as activity-dependent disinhibition dominate network dynamics. The variances of the summed inputs to the epileptic network is proportional to the sum of the input variances, leading to rare surges of the intensity of input. In the case of activity-dependent disinhibition, levels of input above this seizure threshold rapidly degrade inhibition in the epileptic network, leading to further increases network activity. This process culiminates in a seizure.