Computational models of epileptiform activity in single neurons.

A series of original computational models written in NEURON of increasing physiological and morphological complexity were developed to determine the dominant causes of epileptiform behavior. Current injections to a model hippocampal pyramidal neuron consisting of three compartments produced the sustained depolarizations (SD) and simple paroxysmal depolarizing shifts (PDS) characteristic of ictal and interictal behavior in a cell, respectively. Our results indicate that SDs are the result of the semi-saturation of Na+, Ca2+ and K+ active channels, particularly the CaN, with regular Na+/K+ spikes riding atop a saturated depolarization; PDS rides on a similar semi-saturated depolarization whose shape depends more heavily on interactions between low-threshold voltage-gated Ca2+ channels (CaT) and Ca(2+)-dependent K+ channels. Our results reflect and predict recent physiological data, and we report here a cellular basis of epilepsy whose mechanisms reside mainly in the membrane channels, and not in specific morphology or network interactions, advancing a possible resolution to the cellular/network debate over the etiology of epileptiform activity.

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