Changes in inhibitory processes in the hippocampus following recurrent seizures induced by systemic administration of kainic acid

Rats were chronically prepared with stimulation electrodes in the angular bundle and recording electrodes in the dentate gyrus under electrophysiological guidance. Following testing of dentate gyrus field potentials, the animals were given a single injection of kainic acid which caused repeated seizures and led to status epilepticus. The seizures were stopped by administration of a barbiturate anesthetic after 60 min. Changes in inhibition during seizure development were monitored by administering pulse pairs at regular intervals. The results revealed a progressive kainic acid-induced loss in inhibition that preceded the occurrence of seizures. This breakdown of inhibition was transient, and generally disappeared within 24 h. Over subsequent testing, recurrent inhibition, as measured by the double pulse test, increased beyond baseline levels. This increase persisted for at least one month and was restricted to the early phase of inhibition with a conditioning/test pulse interval of less than 50 ms. A later phase of inhibition, measured at interpulse intervals between 200 and 300 ms, showed a transient decrease which lasted about a week. These results contrast with previous reports of a long-term period of hyperexcitability following recurrent seizures. Procedural differences which might account for such discrepancies are discussed.