On the relationship between kainic acid-induced epileptiform activity and hippocampal neuronal damage

Abstract

The electrophysiological effects of kainic acid on evoked hippocampal granule cell activity and recurrent inhibition (as measured with the twin-pulse technique) were examined in urethaneanesthetized rats. In the 3-hr period after injection, kainic acid (10 mg/kg i.v.) caused repetitive cycles of decreased recurrent inhibition, granule cell epileptiform discharges and depression of evoked activity. These electrophysiological effects were accompanied by twitching of the vibrissae, mild hyperpyrexia and “wet-dog” shakes which, despite anesthesia, often occurred at the end of an epileptiform granule cell discharge. Four hours after the injection of kainic acid, recurrent inhibition was abolished and granule cell spike amplitudes in response to perforant path stimuli were significantly greater than saline controlor pre-drug values. Concomitantly, kainic acid caused acute damage to dentate hilar interneurons and to the cell body and proximal apical dendritic regions of CA3 pyramidal cells. These results indicate that an early effect of kainic acid is impairment of recurrent inhibition, possibly as a result of damage to inhibitory interneurons. The presumably resultant epileptiform activity of dentate granule cells and acute damage to the region of the pyramidal cells which receive dense excitatory input from granule cell axon terminals supports the view that epileptiform activity plays a significant role in the neurotoxic effects of kainic acid.