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.

Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp 120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2＋ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gpl20 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment signiifcantly increased the slope of input-output curves in rat neurons after lfuid per-cussion injury. Diazepam signiifcantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the lfuid per-cussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.