阿尔茨海默病小鼠恐惧记忆活动中峰电位与场电位Gamma节律的相关性  

Correlation between Spike and Gamma rhythm of local field potential in Alzheimer's disease mice during fear memory activity

作　　者：赵辉民 王坚基 付焱 高启超 王晨芳 蔡红艳[3] 王昭君[1] Zhao Huimin;Wang Jianji;Fu Yan;Gao Qichao;Wang Chenfang;Cai Hongyan;Wang Zhaojun(Department of Physiology,Key Laboratory of Cellular Physiology,Ministry of Education,Shanxi Medical University,Taiyuan 030001,China;The Second Clinical Medical College,Shanxi Medical University,Taiyuan 030001 y China;Department of Microbiology and Immunology,Shanxi Medical University.Taiyuan 030001^China)

机构地区：[1]山西医科大学生理学系,细胞生理学教育部重点实验室,太原030001 [2]山西医科大学第二临床医学院,太原030001 [3]山西医科大学微免教研室,太原030001

出　　处：《中华行为医学与脑科学杂志》2020年第4期289-295,共7页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目(31600865);山西省“1331工程”重点学科建设计划项目(1331KSC);山西省重点学科建设经费资助项目(FSKSC);山西省高等学校大学生创新创业训练项目(201910114019)。

摘　　要：目的探讨阿尔茨海默病(Alzheimer’s disease,AD)转基因小鼠在恐惧记忆活动中峰电位与场电位Gamma节律之间的内在联系。方法将6月龄APP/PS1/tau三转基因(3xTg)小鼠和野生型(WT)小鼠分为3xTg组和WT组,每组10只。无菌条件下在每组小鼠海马内埋置电极,两周后进行条件恐惧箱的行为学实验。通过小鼠头部埋置的无线遥测装置同步监测分析Gamma节律、Spike和Burst发放频率的变化情况,最后使用熵值计算Gamma节律与Spike的相关性。结果(1)在行为学实验中,3xTg小鼠因条件刺激引起的僵直比率为[(54.07±2.32)%],显著低于WT小鼠[(76.21±2.88)%](t=4.796,P<0.01)。(2)同步记录到WT小鼠在Pre-CS期Gamma节律的功率为[(11.574±1.147)dB],给予CS后上升为[(18.108±1.177)dB](t=3.386,P<0.01)。3xTg组在给予CS之后Gamma功率[(12.346±1.345)dB]明显低于WT组(t=3.423,P<0.01)。(3)WT小鼠在Pre-CS阶段Spike发放频率为[(5.667±1.475)次/s],给予条件刺激后显著升高[(11.008±1.335)次/s](t=3.542,P<0.01)。而3xTg小鼠的Spike发放频率在CS之后为[(5.249±1.033)次/s]明显低于WT组(t=4.788,P<0.01)。(4)WT组在Pre-CS和CS阶段Burst间隔时间分别为[(0.550±0.043)s]和[(1.075±0.034)s],可见WT组Burst发放频率在给予条件刺激之后显著增加(t=5.188,P<0.01)。而3xTg组经过条件刺激后发放间隔为[(0.619±0.033)s],显著低于WT组(t=3.352,P<0.01)。(5)给予条件刺激后,WT小鼠的Spike-Gamma熵值曲线始终高于3xTg小鼠,其中WT组和3xTg组的相关性最高值分别为(0.403±0.031)和(0.314±0.028),3xTg组的Spike-Gamma相关性与WT小鼠相比显著下降(t=3.372,P<0.01)。结论AD恐惧记忆的缺陷可能是由于Spike-LFP(Gamma)发放不协调导致的。Objective To explore the relationship between the Spike and the Gamma rhythm of the local field potential(L F P)in Alzheimer's disease(A D)transgenic mice during fear memory activity.Methods Six-month-old A P P/P S l/tau three transgenic(3xTg)mice and wild-type(W T)mice were divided into 3xTg group and WT group,with 10 mice in each group.The electrodes were embedded into the hippocampus of mice under sterile conditions,and the behavioral experiment of conditioned fear box test was carried out two weeks later.The changes of Gamma rhythm,Spike and Burst firing were recorded and analyzed by the wireless telemetry device which embedded in the mouse head.Finally,the correlation between Gamma rhythm and Spike was calculated by entropy value.Results(1)In behavioral experiments,the freezing ratio caused by conditioned stimulation(CS)in 3xTg mice was((54.07±2.32)%),which was significantly lower than that of WT mice((76.21±2.88)%)(i=4.796,P<0.01).(2)Simultaneously recorded the average power of the Gamma oscillation in the Pre-CS period of the WT mice was((11.574±1.147)dB),which increased to((18.108±1.177)dB)after CS(t=3.386,P<0.01).After CS administration,the average power of Gamma in 3xTg group((12.346±1.345)dB)was significantly lower than that of WT group(t=3.423,P<0.01).(3)The frequency of Spike release in WT mice during the Pre-CS period was((5.667±1 475)tim es/s),significantly increased to((11.008±1.335)tim es/s)after CS(￡=3.54201).The frequency of Spike release of 3xTg mice after CS((5.249±1.033)tim es/s)was significantly lower than that of WT group(t=4.788,P<0.01).(4)The Burst duration of WT group in pre-CS and CS period were((0.550±0.043)s)and((1.075±0.034)s)Respectively.It suggested that the Burst firing frequency of WT group increased significantly after conditional stimulation(t=5.188,P<0.01).However,the release interval of 3xTg group after CS((0 619±0.033)s)was significantly lower than that of WT group(t=3.352,P<0.01).(5)After CS,the Spike-Gamma entropy curve of WT mice was always higher than that

关 键 词：阿尔茨海默病 海马 条件恐惧记忆 无线神经遥测技术 场电位 峰电位 小鼠 

分 类 号：R74[医药卫生—神经病学与精神病学]