Multifocal spontaneous epileptic activity induced by restricted bicuculline ejection in the piriform cortex of the isolated guinea pig brain

Abstract

1. We investigated the development of epileptic activity in the limbic lobe of the in vitro isolated brain preparation after induction of a restricted epileptic focus in the rostral portion of the anterior piriform cortex (APC) by means of local bicuculline ejection. 2. The modifications of the local responses evoked by stimulation of the lateral olfactory tract were consistent with an increase in excitability of layer II pyramidal neurons. The abnormal discharge output of the epileptic focus propagated throughout the piriform cortex (PC) and generated late synaptic stimulus-evoked epileptiform potentials in layer Ib, where corticocortical associative fibers contact the distal dendrites of pyramidal cells. 3. Spontaneous epileptiform potentials (SEPs) originated in the primary focus at the bicuculline ejection site 10–15 min after drug application and propagated via associative fibers to the posterior PC (PPC). 4. Autonomous secondary foci generating SEPs independently from the primary anterior focus developed in the PPC within 2 h after the bicuculline application. 5. Ictal events seldom occurred spontaneously in PC but could be induced by tetanic afferent stimulation. Evoked ictal events in PC had the characteristics of afterdischarges, being short in duration and localized in space and showing a progressively decreasing firing rate. 6. Self-sustained spontaneous ictal discharges were observed in the entorhinal cortex and hippocampus but not in PC after activation of the APC focus. 7. We conclude that in an acute pharmacological model of focal epilepsy, associative corticocortical connections hold a primary role 1) in the propagation of interictal epileptiform activity throughout the limbic lobe and 2) in the generation of secondary epileptic foci. We also demonstrate that self-sustained ictal events are not spontaneously generated in PC, although paroxysmal seizure-like discharges occur in hippocampus. We discuss the relevance of the rostral-to-caudal-directed associative fiber system in generation of limbic seizures.