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。

abstractsObjective:To explore the relationship between the Spike and the Gamma rhythm of the local field potential (LFP) in Alzheimer's disease (AD) transgenic mice during fear memory activity.Methods:Six-month-old APP/PS1/tau three transgenic (3xTg) mice and wild-type (WT) 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)%) ( t=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)times/s), significantly increased to ((11.008±1.335) times/s) after CS ( t=3.542, P<0.01). The frequency of Spike release of 3xTg mice after CS ((5.249±1.033) times/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 of 3xTg mice. The maximum correlation of WT group and 3xTG group were (0.403±0.031) and (0.314±0.028), respectively. The Spike-Gamma correlation of the 3xTg group was significantly lower than WT mice ( t=3.372, P<0.01). Conclusion:The defect of fear memory in Alzheimer's disease may be caused by the disharmony of Spike-LFP (Gamma) distribution.