RAPID KINDLING WITH RECURRENT HIPPOCAMPAL SEIZURES

Kindling is a widely used model of epilepsy. While intriguing hypothes es have recently emerged about how kindling occurs, the mechanisms beh ind kindling remain to be elucidated. In order to test whether certain anatomical changes that have been detected in the brains of animals t hat have completed kindling are necessary for the expression of kindle d seizures, means to achieve kindling over a time course too rapid for the anatomical changes to take place were sought. Stimulus trains of various durations (2 and 10 s) and frequencies (20, 50, and 100 Hz) we re given every 30 min, 12 times a day for 4 consecutive days to rats t hrough bipolar electrodes stereotactically positioned in the ventral h ippocampus. Responses were monitored with conventional kindling behavi oral seizure scores and afterdischarge durations. The frequencies stud ied were chosen to survey the range that has been previously used to d etermine the optimal frequency for eliciting maximal dentate activatio n. Maximal dentate activation is a paroxysmal process that has been po stulated to play both a role in regulating epileptiform activity in th e hippocampus and adjacent regions that are coupled in a functional hi ppocampal-parahippocampal loop and a role in kindling. All types of tr ains resulted in rapid kindling in which kindled motor seizures emerge d after several stimuli and then were consistently elicited with each stimulus; there was also retention of the kindled state after periods of 18 h of withholding the stimuli. Thus, the overall response profile of the rapid kindling demonstrated in this study was phenomenological ly similar to the profile of traditional kindling. Yet rapid kindling developed more quickly than did mossy fiber sprouting, determined in p rior work, thereby excluding the latter as a necessary factor in rapid kindling. Stimulus frequency significantly influenced the rate of rap id kindling. Trains of 20 Hz, the optimal frequency for eliciting maxi mal dentate activation, yielded the fastest kindling. This finding sup ports the proposed role of maximal dentate activation and the hippocam pal-parahippocampal loop in kindling. Longer (10 s) trains consistentl y triggered shorter afterdischarge durations. We postulate that this m ay reflect a tighter linkage between seizure-terminating processes wit h the 10 s trains than with 2 s trains.