Development of spontaneous seizures over extended electrical kindling. II. Persistence of dentate inhibitory suppression

Abstract

The effect of an extended program of perforant path or amygdala kindling on paired-pulse suppression in the dentate gyrus was studied in male hooded rats. Repeated kindling stimulations were delivered twice or three times daily until either 300 stimuli had been delivered or generalized convulsions had been observed to occur spontaneously. Paired-pulse suppression was monitored prior to and over the course of kindling using a standard variable interval paradigm. We also used a variable intensity paradigm in which the intensity of the conditioning pulse was varied while the test pulse intensity was fixed at 600 μA and the interpulse interval was fixed at 30 ms. Both procedures revealed progressive increases in paired-pulse suppression which persisted over the course of kindling. This increased inhibition also persisted in animals which developed spontaneous seizures. The variable intensity paired-pulse procedure also allowed us to monitor facilitation effects which were relatively uncontaminated by recurrent inhibition (when the conditioning pulse intensity was low). Kindling was found to increase paired-pulse facilitation. With the standard variable interval paradigm, these increases in facilitation masked the increases in suppression.