THE EFFECT OF KINDLING BEYOND THE STAGE-5 CRITERION ON PAIRED-PULSE DEPRESSION AND HILAR CELL COUNTS IN THE DENTATE GYRUS

Recent experiments have indicated that recurrent inhibition in the dentate gyrus, as measured with paired-pulse tests, is reduced following the induction of status epilepticus. Also, a loss of cells in the hilus has been reported, and it has been suggested that the two effect might be related. In this experiment, we have monitored paired-pulse depression and counted cells in the hilus in animals that have been kindled well beyond the typical stage 5 criterion. Responses evoked in the dentate gyrus by paired-pulse stimulation of the perforant path were monitored before and after kindling of the perforant path. One group of animals served as controls and received no kindling stimulations. Another group was kindled to 4 stage 5 seizures and then allowed to recover for 2 months. A third group was kindled to 44 stage 5 seizures and then allowed to recover for at least 5 weeks. Paired-pulse tests were taken at 1 week intervals during the kindling and recovery phases. Paired-pulse inhibition increased during kindling, peaked after 4 stage 5 seizures, remained enhanced throughout the additional 40 stage 5 seizures, and recovered towards baseline over a period of about 5 weeks. Upon completion of this phase of the experiment, cell counts were taken in the hilar regions of the Nissl stained brain sections. There was a significant reduction in number of cells in the tissue from kindled animals, compared to controls, but there was no significant difference between the 2 kindled groups. These results indicate that a loss of cells in the hilus due to the repeated induction of epileptiform activity is.not necessarily linked to corresponding losses of inhibition.