Loss of hippocampal interneurons has been reported in patients with se
vere temporal lobe epilepsy and in animals treated with kainate. We in
vestigated the relationship between KA induced epileptiform discharge
and loss of interneurons in hippocampal slice cultures. Application of
KA (1 mu M) produced reversible epileptiform discharge without neurot
oxicity. KA (5 mu M), in contrast, produced irreversible epileptiform
discharge and neurotoxicity, suggesting that the irreversible epilepti
form discharge was required for the neuronal loss. Loss of CA3 pyramid
al cells and parvalbumin-like immunoreactive (PV-I) interneurons prece
ded loss of somatostatin-like immunoreactive (SS-I) interneurons sugge
sting a different time course of KA neurotoxicity in these subpopulati
ons of interneurons.