Sustained electrical stimulation of the perforant path duplicates kainate-induced electrophysiological effects and hippocampal damage in rats.

Electrical stimulation of the perforant path of urethane-anesthetized rats for 24 h evoked hippocampal granule cell population spikes, epileptiform discharges, and abolished the recurrent inhibition of granule cells (as determined with the twin pulse technique). After 24 h of stimulation, hilar interneurons of area dentata and the regions of the CA3 pyramidal cells which receive granule cell input were damaged; 'CA2' pyramidal cells and dentate granule cells were relatively unaffected. Pericellular spaces possibly indicative of acute gliotoxicity were observed in the CA1 pyramidal cell body region. These results establish a causative relationship between excessive presynaptic neuronal activity and postsynaptic neuronal damage.