PERSISTENT HYPEREXCITABILITY IN ISOLATED HIPPOCAMPAL CA1 OF KAINATE-LESIONED RATS

1. Subcutaneous kainate injection in rats evoked acute seizures and led to cell loss in the hilus and areas CA1 and CA3, which resembled the pattern of hippocampal sclerosis often associated with temporal lobe epilepsy in humans. 2. Simultaneous intra- and extracellular recordings were performed in the stratum pyramidale of area CA1 while stimulating in the stratum radiatum close to the recording electrodes. Responses from control slices consisted of a brief excitatory postsynaptic potential (EPSP) with only one action potential, corresponding to a single extracellular population spike, followed by a clear biphasic inhibitory postsynaptic potential (IPSP). In slices from kainate-treated animals, however, stimulation evoked a prolonged EPSP, which often triggered multiple action potentials corresponding to multiple extracellular population spikes. 3. In slices from kainate-treated animals, the mean amplitude but not the duration of the stimulation-evoked IPSP was reduced. The extent of the kainate-induced loss of inhibition in area CA1 was highly variable. 4. Low concentrations of bicuculline in control slices led to a moderate hyperexcitability, which consisted of multiple population spikes and mirrored the responses observed in slices from kainate-treated animals in normal ACSF. Prolonged application of 10-30 muM bicuculline for greater-than-or-equal-to 30 min led to a much higher level of hyperexcitability, which was similar in slices from controls and kainate-treated rats. These findings are consistent with the hypothesis that the hyperexcitability of CA1 pyramidal neurons following kainate treatment is mainly due to decreased GABA(A)- receptor-mediated inhibition and that the loss of inhibition is only partial. 5. Animals that survived the kainate injection for 182-524 days showed the same pattern of cell loss seen in rats studied 41-110 days postlesion. The electrophysiological results in these two groups were not significantly different, however, both differed significantly from controls. 6. We conclude that, although some minor changes might occur, the kainate-induced hyperexcitability in area CA1, present 1-2 mo after the injection, persists for >500 days.