Changes of paired-pulse evoked responses during the development of epileptic activity in the hippocampus

Dysfunction of inhibitory synaptic transmission can destroy the balance between excitatory and inhibitory synaptic inputs in neurons,thereby inducing epileptic activity.The aim of the paper is to investigate the effects of successive excitatory inputs on the epileptic activity induced in the absence of inhibitions.Paired-pulse orthodromic and antidromic stimulations were used to test the changes in the evoked responses in the hippocampus.Picrotoxin(PTX),γ-aminobutyric acid(GABA) type A(GABA A) receptor antagonist,was added to block the inhibitory synaptic transmission and to establish the epileptic model.Extracellular evoked population spike(PS) was recorded in the CA1 region of the hippocampus.The results showed that the application of PTX induced a biphasic change in the paired-pulse ratio of PS amplitude.A short latency increase of the second PS(PS2) was later followed by a reappearance of PS2 depression.This type of depression was observed in both orthodromic and antidromic paired-pulse responses,whereas the GABAergic PS2 depression [called paired-pulse depression(PPD)] during baseline recordings only appeared in orthodromic-evoked responses.In addition,the depression duration at approximately 100 ms was consistent with a relative silent period observed within spontaneous burst discharges induced by prolonged application of PTX.In conclusion,the neurons may ignore the excitatory inputs and intrinsically generate bursts during epileptic activity.The depolarization block could be the mechanisms underlying the PPD in the absence of GABA A inhibitions.The distinct neuronal responses to stimulations during different epileptic stages may implicate the different antiepileptic effects of electrical stimulation.