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 ep ilepsies. Whether ISs are causally involved or represent protective element s in the transition toward an ictal discharge is an open question. Previous studies suggested that inhibition or disfacilitation occurs during the per iod elapsing between two ISs induced by local application of either bicucul line or penicillin in the piriform cortex of the in vitro isolated guinea p ig brain preparation. We further investigated this issue by studying respon ses to afferent stimulation during the interspike period (6.3 +/- 2.5 s; me an +/- SD). Properly set stimulation intensity of the lateral olfactory tra ct 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 exis tence of a period of enhanced threshold to stimulus-evoked activation that coincides with the interspike interval in the absence of stimulation. Curre nt 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 cou ld play a protective role or at least provide an effective restraint agains t the onset of a focal ictal discharge.