SELECTIVE LOSS OF EARLY SUPPRESSION IN THE DENTATE GYRUS PRECEDES KAINIC ACID-INDUCED ELECTROGRAPHIC SEIZURES

The role of inhibitory and facilitatory processes in the induction of seizures was studied in a kainic acid (KA) model of epilepsy. The dent ate gyrus (DG) response to paired-pulse stimulation of the perforant p ath (PP) was monitored prior to and immediately following the initial KA induced afterdischarge (AD) in rats chronically prepared with stimu lation recording electrodes. The subjects received a 1-h program of st imulation consisting of repeated sequences of pulse pairs at a short ( 20-30 ms), intermediate (45-90 ms), and long (200-300 ms) interpulse i nterval (IPIs). The stimulation program was administered both under co ntrol conditions and immediately following systemic injection of KA. D uring the control condition, stable suppression of population spike me asures was obtained at the short (early phase) and long (late phase) I PIs, while facilitation was observed at the intermediate IPI. Administ ration of KA resulted in a progressive loss of suppression prior to th e initial AD at the short IPI; neither facilitation nor the late phase of suppression were significantly affected. The early phase decreased further following the initial discharge. Since the early phase most l ikely reflects recurrent inhibition, these results provide evidence th at inhibitory loss precedes the occurrence of KA induced AD, and that this inhibitory loss is increased further following the initial evoked AD. A use-dependent disinhibition is one possible explanation for the change in responsiveness that precedes the AD. This disinhibition cou ld result from a depressed response at GABA-A receptors, an increased responsiveness at GABA-B receptors or possibly both. (C) 1998 Elsevier Science B.V. All rights reserved.