The Discussion Of Intracellular Signaling Mechanisms On Gamma Oscillation In Hippocampus

BackgroundGamma(γ)oscillation,a hallmark of neuronal network function,Which is present in multiple brain regions,is produced by the interaction between the internneurons and pyramidal neurons of brain network,and is significantly enhanced in the high attention,exploration behavior and learning and memory activities.γ oscillation reflects high brain functions,and has been extensively studied as a putative mechanism underlying learning and memory.Disruption of γ oscillation occurred in neurodegenerative diseases,such as Alzheimer’s disease(AD).And recent research has reported that γ rhythms reduced Aβproduction in hippocampus of AD mice.Intrcellular signal molecules such as cAMP/ PKA(cyclic-AMP-dependent protein kinase),PI3 kinase/AKT(PKB),PKC(protein kinase C),and kinases such as AMPK(AMP-activated protein kinase)and HDAC(histone decetylase),play important roles in synaptic transmission and synaptic plasticity,but whether there are involved in the modulation of γ oscillation is not clear.Our study aims to investigate the role of these intrcellular signal molecules and kinases on γ oscillation,in order to fully understand the controllable factors of γ oscillation and provide new ideas and therapeutic targets for clinical diseases related to impaired learning and memory functions.ObjectivesTo investigate the effects of intracellular signaling molecules and kinases on γoscillation in hippocampus.Methods1 field potential recording4 to 6 weeks of male SD rats were sacrificed with 10% chloral hydrate,and theprecooling(0℃)of ACSF-cutting solution were used to perfuse through the left ventricle system until the limbs were white.Next the brain tissue was quickly removed and fixed,then sliced horizontally(350μm).Transferring hippocampal slices to the interficial bath perfusion system rapidly.After incubation 60 minutes,stable and lasting γ oscillation were induced by KA and recorded by extrcellular microelectrode.2 Observing the effects of intrcellular kinases inhibitors on area power and peak frequency of γ oscillation induced by KA.3 The data were analyzed by Spike 2,analyzed by Sigmastat.All datas are expressed as mean ± standard error of mean.If P ≤ 0.05,it is considered significant statistically.Results1 AC inhibitor MDL,PKA inhibitor H89,PKC inhibitor G6983,ERK1/2 inhibitor U0126,had no obvious effect on KA-induced γ oscillation.2 Akt inhibitor TCBN not PI3 K inhibitor Wortmannin increased γ-oscillation power(P<0.05).3 AMPK inhibitor CC enhanced γ-oscillation power(P<0.01).4 Nonspecific-HDAC inhibitor SAHA enhanced γ-oscillation power and selectiveHDACI inhibitor PD106(P<0.001)and the specific-HDAC6 inhibitor NXT increasedγ-oscillation power(P<0.05).ConclusionsHippocampus γ oscillation involves the activations of Akt,HDAC and AMPK,and their activations have a negative effect on γ oscillation,suggesting that the γ oscillation has self-regulation mechanism.AC,PKA,ERK,PI3 K,PKC do not participate in γ oscillation induced by KA in hippocampus.