Alterations in both excitation and inhibition occur before the onset of seizure activity in the hippocampus

Abstract

Excitatory and inhibitory mechanisms have been implicated in the onset of seizures and as underlying kindling. In this study, changes in responses to single stimuli and paired pulse stimuli were used to monitor postsynaptic excitability before the onset of seizure activity in limbic circuits of urethane-anesthetized rats. With sufficient stimulus intensity, a stimulus paradigm of seven pulses every second for 10 s led to seizure activity, as indicated by the appearance of maximal dentate activation, and afterdischarges. An increase in the evoked response was found in both CA1 and the dentate gyrus during stimulus trains to either CA3 or the angular bundle and there was the appearance of a polysynaptic response. There was an increase in paired pulse inhibition in the dentate gyrus and a decrease in paired pulse inhibition in the CA1 region during the stimulus protocol. Since repeated seizures and a number of pharmacological agents are known to alter the onset and duration of seizure activity, a relationship between the changes in excitability and the onset of the seizure activity was tested using MK-801, ketamine, bicuculline, diazepam, phenobarbital, baclofen and repeated seizures. Overall, alteration of the amplitude of the polysynaptic response in CA1 to angular bundle stimulation correlated best with the effects of the drugs and the seizures on the duration of maximal dentate activation.