CELLULAR MECHANISMS UNDERLYING SPONTANEOUS INTERICTAL SPIKES IN AN ACUTE MODEL OF FOCAL CORTICAL EPILEPTOGENESIS

The cellular mechanisms involved in the generation of spontaneous epil eptiform potentials were investigated in the pirifom cortex of the in vitro isolated guinea-pig brain. A single, unilateral injection of bic uculline (150-200 nmol) in the anterior piriform cortex induced locall y spontaneous interictal spikes that recurred with a period of 8.81 +/ - 4.47 s and propagated caudally to the ipsi- and contralateral hemisp heres. Simultaneous extra- and intracellular recordings from layer II and III principal cells showed that the spontaneous interictal spike c orrelates to a burst. of action potentials followed by a large afterde polarization. Intracellular application of the sodium conductance bloc ker, QX-314 (80 mM), abolished bursting activity and unmasked a high-t hreshold slow spike enhanced by the calcium chelator EGTA (50 mM). The slow spike was abolished by membrane hyperpolarization and by local p erfusion with 2 mM cadmium. The depolarizing potential that followed t he primary burst was reduced by arterial perfusion with the N-methyl-D -aspartate receptor antagonist, DL-2-amino-5-phosphonopentanoic acid ( 100-200 mu M). The non-iv-methyl-D-aspartate glutamate receptor antago nist, 6-cyano-7-nitroquinoxaline-2,3-dione (20 mu M), completely and r eversibly blocked the spontaneous spikes. The interictal spikes were t erminated by a large afterpotential blocked either by intracellular QX -314 (80 mM) or by extracellular application of phaclofen and 2-hydrox ysaclofen (10 and 4 mM, respectively). The present study demonstrates that, in an acute model of epileptogenesis, spontaneous interictal spi kes are fostered by a primary burst of fast action potentials that rid e on a regenerative high-threshold, possibly calcium-mediated spike, w hich activates a recurrent, glutamate-mediated potential responsible f or the entrainment of adjacent and remote cortical regions. The bursti ng activity is controlled by a GABA(B) receptor-mediated inhibitory sy naptic potential. (C) 1998 IBRO. Published by Elsevier Science Ltd.