KINDLING-INDUCED EPILEPTIFORM POTENTIALS IN PIRIFORM CORTEX SLICES ORIGINATE IN THE UNDERLYING ENDOPIRIFORM NUCLEUS

1. Previous studies in vivo and in vitro have shown that kindling from several locations in the limbic system induces the onset of epileptif orm activity in the piriform (olfactory) cortex in the rat. In the pre sent study we tested the hypothesis that kindled epileptiform events i n piriform cortex are initiated in the underlying endopiriform nucleus . The experiments were performed in slices taken from rats that were p reviously kindled by conventional means. 2. Both stimulus-evoked and s pontaneous interictal-like epileptiform events were observed in most s lices from the anterior piriform cortex, but in few slices from the po sterior piriform cortex. These events resembled those described in una nesthetized and urethan-anesthetized rats in previous studies. 3. Find ings in support of the hypothesis were as follows. Epileptiform events in the endopiriform nucleus preceded those in the piriform cortex. Ep ileptiform events could occur in endopiriform nucleus alone, but were only observed in the piriform cortex following occurrence in the endop iriform nucleus. A buildup in population activity preceded the onset o f all-or-none epileptiform events in the endopiriform nucleus. Epilept iform events could be triggered by local application of glutamate in t he endopiriform nucleus and adjacent claustrum, but not from the pirif orm cortex. Finally. local application of Co2+ in the endopiriform nuc leus, but not in the piriform cortex or elsewhere in the slices, block ed the occurrence of epileptiform events. 4. Additional experiments we re performed to further characterize the generation process. 6,7-Dinit roquinoxaline-2,3-dione (DNQX) blocked epileptiform events and the pre ceding accelerating buildup in multiunit activity at a concentration b elow that required to block the monosynaptic excitatory postsynaptic p otential (EPSP). This suggests that EPSPs mediated by lpha-amino-3-hyd roxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors underlie epil eptiform events in slices of piriform cortex, and that multisynaptic i nteractions within the endopiriform nucleus are required for generatio n of these epileptiform EPSPs. By contrast, block of N-methyl-D-aspart ate (NMDA) receptors decreased the amplitude of epileptiform EPSPs but did not block their occurrence, indicating that NMDA receptors contri bute to generation but are not required. When membrane potential was d epolarized to increase driving force, fast inhibitory postsynaptic pot entials were found to consistently accompany the buildup process and e pileptiform EPSPs. This indicates that if initiation of epileptiform a ctivity in the endopiriform nucleus results from a compromise in feedb ack inhibition, this compromise is partial rather than complete. 5. Ep ileptiform EPSPs in slices of piriform cortex from kindled rats displa yed similarities in properties, locus of origin, and mechanism of gene ration to those previously studied in slices from normal rats in which epileptiform activity was induced by a brief period of bursting activ ity. These similarities suggest that study of bursting-induced epilept iform EPSPs may provide insight into certain aspects of kindling-induc ed epileptogenesis.