Molecular mechanisms of epilepsy

The term ‘seizure’ emphasizes the abrupt and unpredictable nature of the onset of epochs of pathological neuronal synchrony that define the disorder of epilepsy. Mechanisms of epilepsy should account for seizure transitions with these unique temporal properties. In this review, Kevin Staley discusses how combining insights from new genetic etiologies with seizure timing may begin to outline the mechanisms by which the brain becomes predisposed to seizures. 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.