The Effect And Mechanism Of Compound C On Gamma Oscillation Of Hippocampus In Mice

BackgroundSynchronous network oscillations at gamma frequency band in hippocampal neuronal network are closely related to advanced brain functions such as cognition,learning,and memory.Gamma is mainly produced by fast-spiking interneurons,and highly sensitive to mitochondrial function such as ATP concentration.Adenylate-dependent protein kinase(AMPK)is a sensor for energy metabolism.The increase of AMP/ATP ratio can promote the activation of AMPK and regulate the energy metabolism.However,it is not clear whether AMPK activation affects γ oscillation.Therefore,to explore the effects of AMPK on gamma rhythm is of great significance for the understanding the role of AMPK on cognitive function under physiological conditions.ObjectiveThe aim of this study is to investigate the effects and mechanisms of AMPK on the hippocampal gamma oscillations.MethodsWe recorded the gamma oscillations induced by carbachol and kainate by using field potential recording.Western blot was used to assay the expression level of AMPK/ p-AMPK in the mouse hippocampus.The synaptic current was recorded by the whole-cell patch clamp.Results 1.AMPK inhibitor,Compound C,enhanced the power and dominant frequency of gamma oscillation induced by either CCH or KA in the area of hippocampal CA3.2.AICAR,one of the AMPK agonists,had no effect on the gamma oscillations induced by carbachol.3.CCH enhanced amplitude without affecting the frequency of s IPSP in hippocampal CA3 neurons;application of AMPK inhibitor,Compound C in the presence of CCH,enhanced the frequency without affecting the amplitude of sIPSC.4.CCH reduced amplitude and frequency of sEPSC in the hippocampal CA3 neurons;application of AMPK inhibitor,Compound C in the presence of CCH,had no effect on either the frequency or the amplitude of sEPSC.5.Western blot analysis showed that CCH inhibited the expression of the p-AMPK,but not that of AMPK.ConclusionAMPK inhibitor concentration-dependently enhances the power and dominant frequency of gamma oscillation in the area of hippocampal CA3,and does not have model specificity.AMPK inhibitor enhances gamma oscillation by selectively activating GABA neurons to increase the frequency of the sIPSC.