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无线神经遥测技术在阿尔茨海默病转基因小鼠恐惧学习记忆活动中的应用——海马Theta节律观察

胡梦明, 闫旭东, 张秀敏, 白羽, 赵芳, 祁金顺^*

山西医科大学生理学系，太原 030001

摘要

APP/PS1/tau三转基因(3xTg)小鼠是国际公认的阿尔茨海默病(Alzheimer’s disease, AD)动物模型，其6月龄时即可表现出与海马相关的认知活动障碍及电生理指标异常，但同步记录AD小鼠行为学和脑电活动的研究仍鲜有报道。近年来，无线遥测技术的发展为同步记录小动物行为和脑电活动创造了条件。本研究利用无线神经遥测技术，结合行为学检测手段，同步记录了3xTg AD小鼠在恐惧记忆活动过程中的行为学表现和海马Theta节律变化，以期揭示AD时认知功能障碍与Theta节律的关系。结果显示：(1)恐惧学习训练阶段，3xTg小鼠与野生型(wild type, WT)小鼠相比，行为学和脑电活动均无明显差异；(2)记忆检测阶段，3xTg小鼠因条件刺激(conditioning stimulus, CS)引起的僵直比率显著低于WT小鼠；(3)条件刺激前(Pre-CS)与CS期间3xTg小鼠海马Theta节律的峰值功率均明显低于WT小鼠；(4) CS可有效提高WT小鼠海马CA1区Theta节律的峰值频率，而这一刺激对3xTg小鼠无效。以上结果表明，3xTg小鼠在认知行为障碍即恐惧学习记忆能力下降的同时，伴有海马CA1区Theta节律的发放频率与发放功率降低。据此推测，Theta节律活动的衰减与3xTg小鼠恐惧记忆行为障碍有关，增强海马Theta节律可能有助于认知行为的改善。

关键词： 无线神经遥测; APP/PS1/tau转基因小鼠; 行为电生理; 恐惧记忆; Theta节律

分类号：Q4-33

Application of wireless neuronal recording system in fear conditioning of Alzheimer’s disease mice — hippocampal Theta oscillation observation

HU Meng-Ming, YAN Xu-Dong, ZHANG Xiu-Min, BAI Yu, ZHAO Fang, QI Jin-Shun^*

Department of Physiology, Shanxi Medical University, Taiyuan 030001, China

Abstract

APP/PS1/tau triple transgenic (3xTg) mouse is a classical animal model of Alzheimer’s disease (AD), which has abnormalities in recognition and electrophysiological properties at early 6-month-old age. However, few studies were performed by using simultaneously recording cognitive behavior and brain electrical activity in the conscious 3xTg mice. By using a new wireless recording system, we recorded hippocampal Theta oscillations in 3xTg mice during the process of fear conditioning test. The results showed that: (1) in training session, no significant difference in the fear behavior and hippocampal Theta activity was found between 3xTg mice and WT mice; (2) in test session, 3xTg mice showed a significant decrease in freezing ratio compared with WT mice when they were exposed to conditioning stimulus (CS); (3) the 3xTg mice showed lower peak power in Theta oscillation in both Pre-CS and CS duration compared with WT mice; (4) CS effectively induced an increase in the peak frequency of Theta oscillation in WT mice, but not in 3xTg mice. These results indicated that the impairment of cognition behavior in 3xTg mice was accompanied with the decreased peak power and peak frequency of Theta oscillation in the hippocampus, suggesting that a decline in Theta oscillation might be involved in the impairments of the fear conditioning, and the enhanced hippocampal Theta oscillation may be beneficial for improving AD cognitive function. 

Key words: wireless neuronal recording; APP/PS1/tau 3xTg mouse; behavioral electrophysiology; fear memory; Theta oscillation

收稿日期：2018-03-24　　录用日期：2018-06-11

通讯作者：祁金顺　　E-mail: jinshunqi2009@163.com

DOI: 10.13294/j.aps.2018.0045

引用本文：

胡梦明, 闫旭东, 张秀敏, 白羽, 赵芳, 祁金顺. 无线神经遥测技术在阿尔茨海默病转基因小鼠恐惧学习记忆活动中的应用——海马Theta节律观察[J]. 生理学报 2018; 70 (5): 571-578.

HU Meng-Ming, YAN Xu-Dong, ZHANG Xiu-Min, BAI Yu, ZHAO Fang, QI Jin-Shun. Application of wireless neuronal recording system in fear conditioning of Alzheimer’s disease mice — hippocampal Theta oscillation observation. Acta Physiol Sin 2018; 70 (5): 571-578 (in Chinese with English abstract).