Spontaneous and stimulation-induced synchronized burst afterdischarges in the isolated CA1 of kainate-treated rats

C. L. Meier and F. E. Dudek Mental Retardation Research Center, UCLA School of Medicine 90024, USA. 1. Kainate treatment preferentially kills dentate hilar neurons and CA3 pyramidal cells and ultimately leads to a chronic epileptic state. Bicuculline-induced epileptiform bursts were studied to test the hypothesis that multiple kainate injections and consequent status epilepticus would lead-after weeks to months of recovery-to prolonged synchronous afterdischarges in the isolated CA1 area of rat hippocampal slices, as would be expected if new recurrent excitatory circuits had formed. 2. Synaptic responses evoked in CA1 pyramidal cells of rats injected subcutaneously with kainate (10 hourly injections, 5 mg/kg each) 24-316 days before the slice experiment were compared with responses in slices from untreated and saline-injected controls. The maximal response to stratum radiatum stimulation in normal solution consisted of two to eight population spikes. 3. When gamma-aminobutyric acid-A receptor-mediated inhibition was reduced with bicuculline, synchronized burst afterdischarges after the initial stimulation-evoked burst, similar to the type of activity described in area CA3 under conditions where inhibition is impaired, occurred in 23% of slices. 4. The prolonged synchronized burst afterdischarges in the isolated CA1 area of kainate-treated rats were associated with large excitatory postsynaptic potentials (EPSPs). These prolonged bursts were not graded with the stimulus intensity; rather, they were triggered in an all-or-none manner, even though there was some variability across bursts. The bursts of population spikes also were correlated with subthreshold EPSPs. 5. Slices that had synchronized burst afterdischarges had significantly more damage in area CA3 than slices without afterdischarges. 6. The data indicate that kainate-induced damage in CA3 can lead to prolonged synchronous afterdischarges, even after CA1 is surgically isolated from the CA3 area. Because the repetitive bursts during the prolonged and synchronous afterdischarges were associated with large EPSPs, these data suggest that kainate-induced damage to CA3 and subsequent degeneration of synaptic terminals in the CA1 area causes the formation of new recurrent excitatory circuits that could be involved in the development of chronic epilepsy.