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创伤后应激障碍对小鼠背侧及腹侧海马谷氨酸能和GABA能神经元兴奋性的影响

刘冬播^1,*, 石彦², 郑申平³, 周浩然³, 赵立维³

¹蚌埠医学院人体解剖学教研室，蚌埠 233030；²蚌埠医学院第一附属医院超声医学科，蚌埠 233004；³蚌埠医学院临床医学院，蚌埠 233030

摘要

本研究旨在通过检测创伤后应激障碍(post-traumatic stress disorder, PTSD)小鼠背侧海马(dorsal hippocampus, dHPC)及腹侧海马(ventral hippocampus, vHPC)神经元电生理特性的改变，探讨海马神经元的可塑性与PTSD后记忆之间的关系。随机将C57Thy1-YFP/GAD67-GFP品系雄性小鼠分为对照组和PTSD组，通过对小鼠施加不可逃避足底电击(foot shock, FS)建立PTSD模型，利用Morris水迷宫探查小鼠空间学习记忆的变化，在全细胞记录模式下检测dHPC和vHPC谷氨酸能神经元和GABA能神经元电生理特性的变化。结果显示：FS可显著降低小鼠平均移动速度、提高僵立次数和僵立百分比；PTSD可显著延长定位逃避训练中的定位逃避期，缩短定位探查训练中在原象限内游泳停留时间，延长在对侧象限内游泳停留时间；FS同时提高dHPC谷氨酸能神经元和vHPC GABA能神经元能障、绝对不应期和动作电位间距，降低dHPC GABA能神经元和vHPC谷氨酸能神经元能障、绝对不应期和动作电位间距。以上结果表明：PTSD损害了小鼠空间感知和学习记忆能力，下调dHPC的整体兴奋性，上调vHPC的整体兴奋性，提示PTSD对小鼠空间记忆能力的影响可能与海马不同亚区神经元的可塑性变化和调控有关。

关键词： 创伤后应激障碍; 谷氨酸能神经元; GABA能神经元; 水迷宫; 小鼠

Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice 

LIU Dong-Bo^1,*, SHI Yan², ZHENG Shen-Ping³, ZHOU Hao-Ran³, ZHAO Li-Wei³

¹Department of Anatomy, Bengbu Medical College, Bengbu 233030, China；²Department of Ultrasound Medicine, the First Affiliated Hospital, Bengbu Medical College, Bengbu 233004, China；³School of Clinical Medicine, Bengbu Medical College, Bengbu 233030, China

Abstract

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.

Key words: post-traumatic stress disorder; glutamatergic neuron; GABAergic neuron; water maze; mouse

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通讯作者：刘冬播　　E-mail: liudongbo@bbmc.edu.cn

引用本文：

刘冬播, 石彦, 郑申平, 周浩然, 赵立维. 创伤后应激障碍对小鼠背侧及腹侧海马谷氨酸能和GABA能神经元兴奋性的影响[J]. 生理学报 2023; 75 (3): 369-378.

LIU Dong-Bo, SHI Yan, ZHENG Shen-Ping, ZHOU Hao-Ran, ZHAO Li-Wei. Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice . Acta Physiol Sin 2023; 75 (3): 369-378 (in Chinese with English abstract).