Discharge threshold is enhanced for several seconds after a single interictal spike in a model of focal epileptogenesis.

Interictal spikes (ISs) are typically observed between seizures in focal epilepsies. Whether ISs are causally involved or represent protective elements in the transition toward an ictal discharge is an open question. Previous studies suggested that inhibition or disfacilitation occurs during the period elapsing between two ISs induced by local application of either bicuculline or penicillin in the piriform cortex of the in vitro isolated guinea pig brain preparation. We further investigated this issue by studying responses to afferent stimulation during the interspike period (6.3 +/- 2.5 s; mean +/- SD). Properly set stimulation intensity of the lateral olfactory tract resets ISs exclusively (and not before) 4-10 s (5.6 +/- 2.0 s; mean +/- SD) after a preceding spontaneous spike. This finding demonstrates the existence of a period of enhanced threshold to stimulus-evoked activation that coincides with the interspike interval in the absence of stimulation. Current source density analysis of depth laminar profiles demonstrated that both stimulus-evoked and spontaneous ISs were generated by the activation of an identical cortical circuit. Our study suggests that interictal spiking could play a protective role or at least provide an effective restraint against the onset of a focal ictal discharge.