The lateral spread of epileptiform discharges in rat neocortical slices: effect of focal phencyclidine application.

Abstract

In vitro and in vivo brain slice techniques were used to examine phencyclidine (PCP) effects on the lateral propagation of epileptiform field potentials (EFP) across adjacent areas of rat frontal neocortex. Epileptiform activity was induced by perfusing slices with Mg 2+-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP were obtained from four microelectrodes placed 2-3 mm apart across coronal slices in the third layer. PCP, applied focally between recording sites, blocked rapid propagation across treated areas and resulted in the emergence of spatially separate, independent pacemakers. The characteristics of paroxysmal depolarization shifts did not change significantly by the blockade of lateral propagation of EFP. The same asynchronized pattern of EFP conduction was observed after local application of the N-methyl-D-aspartate (NMDA)-receptor antagonist DL-2-amino-5-phosphono-valeric acid. Local administration of haloperidol as well as NMDA before PCP application reversibly prevented appearance of multiple pacemakers. Focal application of dopamine produced an abnormal pattern of lateral conduction of EFP in 50 % of tested slices. Pacemaker failure as an indicator of functional impairment of cortical integration is the proposed mechanism for developing of schizophrenia-like psychosis associated with epilepsy. Abbreviations. APV: DL-2-amino-5-phosphono-valeric acid EEG:electroencephalogram EFP:epileptiform field potentials NMDA:N-methyl-D-aspartate PCP:phencyclidine SLPE:Schizophrenialike psychosis associated with epilepsy