Mechanisms of interictal epileptogenesis.

The interictal discharge is a brief epileptiform event that provides the simplest experimental system available for investigating some of the basic mechanisms of epilepsy. Interictal discharges are characterized by two major abnormal properties: each involved neuron exhibits a transient large amplitude depolarization (the "depolarization shift") associated with repetitive spike generation, and this excitation arises with virtual synchrony in the majority of cells in a local population. Recent studies have attempted to define the cellular properties that predispose a cortical circuit to this pathological behavior. There appear to be three general factors that interactively determine cortical susceptibility to epilepsy: Intrinsic membrane properties of neurons. The intrinsic excitability of individual cells may vary greatly within a cortical area; the initiation of a synchronous discharge usually occurs in the subpopulation of cells that has the endogenous ability to generate bursts of action potentials. Efficacy of local inhibitory synaptic mechanisms. Normal integrative functions of the cortex require robust inhibition; depression of inhibition is one of the most reliable ways to trigger a seizure. Effectiveness of excitatory synaptic connections and other synchronizing mechanisms. Highly synchronized discharge among a large number of neurons requires widely divergent excitatory interactions. Differences in these factors for different cortical areas can confer relative susceptibility or resistance to development of epileptiform discharge. Pharmacologic, pathologic, developmental, and genetic processes can presumably mitigate or aggravate focal cortical epileptogenesis by affecting any of these three general factors.