Cellular Mechanisms Of Acute Ethanol Exposure-Induced Down-regulation Of Gamma Network Oscillations In Rat Hippocampal CA3 Area

BackgroundGamma oscillation is rhythmic, synchronized activity within neuronal network generated by interaction between pyramidale neurons and interneurons, occurs in multiple regions, such as hippocampus, and is associated with higher brain function such as learning and memory. Acute ethanol exposure at a dose range reached intoxication (50-200mM) activates dopamine receptor (DR1), PKA via a cascade of DR1-PKA signaling and is associated with impaired NMDA receptor function and synaptic transmission and plasticity. Though ethanol inhibits the cognitive function, its roles on gamma oscillations remain unknown.ObjectivesTo investigate the effects of acute alcohol exposure on hippocampal gamma oscillation, and the possible mechanisms related to the intracellular signals.Methods1 field potential recording(1) 3-4 weeks male SD rats were anesthesied by chloral hydrate and perfused cardiacally with precooling(0℃) of ACSF-cutting solution. The brain was quickly removed and sliced horizontally(400μm).(2) Moving brain slices into interface chamber using a stainless steel spoon and incubated 60 min before an extracellular microelectrode recording. Kainate was used to induce to gamma oscillation.2 The effects of ethanol (50～100 mM) on gamma oscillations were tested, and the effects of DR, NMDA receptor antagonists and various kinase inhibitors as well as HDAC inhibitor on the role of ethanol’s inhibition of gamma oscillation were investigated.All the data were analyzed by Spike 2 software. All statistical tests were performed using SigmaStat software. Results are expressed as mean ± standard error. Measures were considered statistically significant if P<0.05.Results1 Ethanol inhibited gamma oscillation in a dose-dependent manner.2 DR1 antagonist 10μM SCH23390 can partially block the effects of ethanol on gamma oscillation.3 PKA inhibitor H89 significantly reduced ethanol-induced inhibition on gamma power4 ERK and PI3 kinase inhibitors U0126 and wortmannin had no effect on ethanol’s role.5 NMDA receptor antagonist D-AP5 did not prevent but rather enhanced ethanol inhibition of gamma oscillation.6 Histone deacetylase (HDAC) inhibitor SAHA itself increased gamma power, partially blocked the role of ethanol at 50 mM.ConclusionsAcute ethanol reversibly inhibited the hippocampal gamma oscillation, which is related to the activation of the DR-PKA pathway and the inhibition of NMDA erceptor.