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急性恐惧应激对小鼠空间记忆能力和内侧前额叶皮层神经元可塑性的影响

刘冬播^1,*, 石彦², 陈传好¹, 陶恒¹, 卢兴浩¹, 陆进¹

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

摘要

本研究旨在通过检测急性恐惧应激对小鼠空间检索能力以及内侧前额叶皮层(medial prefrontal cortex, mPFC)神经元可塑性的影响，探讨mPFC神经元可塑性变化与应激后记忆调节之间的关系。选取6周龄雄性C57BL/6品系小鼠，随机分成对照组和应激组，对应激组小鼠足底施加电流刺激以建立急性恐惧应激模型，通过Morris水迷宫检测小鼠空间记忆的改变，通过全细胞记录检测边缘前皮质(prelimbic cortex, PrL)和边缘下皮质(infralimbic cortex, IL)锥体神经元和GABA能神经元动作电位发放的变化。结果显示：与对照组相比，急性恐惧应激可显著提高小鼠僵直百分比、僵直次数，降低平均速度，缩短获得性定位训练中的定位潜伏期，增加空间探查训练中在第一象限内探查停留时间，缩短在第三象限内探查停留时间，同时可显著提高小鼠PrL区GABA能神经元和IL区锥体神经元动作电位间距、能障和绝对不应期，降低PrL区锥体神经元和IL区GABA能神经元动作电位间距、能障和绝对不应期。以上结果表明：急性恐惧应激增强了小鼠空间记忆的学习和巩固能力，上调PrL兴奋性和功能，下调IL兴奋性和功能，提示应激后mPFC亚区的可塑性变化可能对空间记忆学习过程有一定的调控作用。

关键词： 恐惧; GABA能神经元; 锥体神经元; 全细胞记录; 小鼠

Effects of acute fear stress on spatial memory and neuronal plasticity in the medial prefrontal cortex in mice

LIU Dong-Bo^1,*, SHI Yan², CHEN Chuan-Hao¹, TAO Heng¹, LU Xing-Hao¹, LU Jin¹

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

Abstract

The purpose of this study was to investigate the effects of acute fear stress on the spatial memory and neuronal plasticity of medial prefrontal cortex (mPFC) neurons in mice, and to elucidate the mechanisms underlying mPFC plasticity and post-stress memory regulation. Male C57BL/6 mice (6 weeks old) were randomly divided into control group and stress group. Foot shock stress was applied to establish an acute fear stress model. Changes in spatial memory were examined by the Morris water maze test, and the dynamic changes in the spike encoding of pyramidal neurons and GABAergic neurons in the prelimbic cortex (PrL) and infralimbic cortex (IL) of mPFC were detected by whole-cell recording. The results showed that acute fear stress significantly enhanced the percentage of freezing and the number of freezing, reduced the average speed, decreased the escape latency during acquisition phase, extended the probing time in the first quadrant and shortened the probing time in the third quadrant during probe trial, increased inter-spike interval, energy barrier and absolute refractory period of GABAergic neurons in the PrL and pyramidal neurons in the IL, while decreased inter-spike interval, energy barrier and absolute refractory period of pyramidal neurons in the PrL and GABAergic neurons in the IL. These results suggest that acute fear stress can enhance the spatial memory of mice, elevate the excitability and function of the PrL, while deteriorate the excitability and function of the IL, and the underlying mechanism may involve the role of mPFC microcircuitry plasticity in spatial memory after stress.

Key words: fear; GABAergic neuron; pyramidal neuron; whole-cell recording; mouse

收稿日期：　　录用日期：

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

DOI: 10.13294/j.aps.2022.0075

引用本文：

刘冬播, 石彦, 陈传好, 陶恒, 卢兴浩, 陆进. 急性恐惧应激对小鼠空间记忆能力和内侧前额叶皮层神经元可塑性的影响[J]. 生理学报 2022; 74 (5): 705-714.

LIU Dong-Bo, SHI Yan, CHEN Chuan-Hao, TAO Heng, LU Xing-Hao, LU Jin. Effects of acute fear stress on spatial memory and neuronal plasticity in the medial prefrontal cortex in mice. Acta Physiol Sin 2022; 74 (5): 705-714 (in Chinese with English abstract).