CUMS对焦虑小鼠海马与前额叶皮层锥体神经元兴奋/抑制平衡的影响

Effects of CUMS on excitatory/inhibitory balance of hippocampal and prefrontal cortex pyramidal neurons in anxiety-like mice

目的:探索慢性不可预见性温和性刺激(CUMS)所致焦虑障碍小鼠额叶皮层与海马锥体神经元兴奋/抑制(E/I)平衡的变化。方法:24只C57/BL6雄性小鼠随机区组分为对照组(CTRL)与模型组(CUMS),每组12只。CUMS组小鼠进行为期21 d的应激,包括束缚1 h、昼夜颠倒24 h、温水强迫游泳5 min、禁食/禁水24 h、潮湿环境饲养18 h、摇晃鼠笼30 min、白噪音1 h、社交应激10 min,CTRL组小鼠正常饲养。随后进行焦虑相关行为学及全细胞记录检测。结果:与CTRL组比较,CUMS组小鼠旷场试验中进入中央区时间明显减少(P<0.01),高架十字迷宫实验中进入开臂的时间明显减少(P<0.01)、次数明显减少(P<0.01),闭臂停留时间明显增加(P<0.01),小鼠dlPFC、mPFC、vCA1锥体神经元sEPSC频率、电容量与E/I比值均明显增加(P<0.01),sEPSC幅度、sIPSC频率、幅度、电容量均无明显改变(P>0.05);而小鼠dCA1锥体神经元sEPSC与sIPSC的频率、幅度、电容量及E/I比值,则均无明显改变(P>0.05)。结论:CUMS所致小鼠焦虑样行为,可能是多脑区参与的结果,主要与dlPFC、mPFC、vCA1脑区的锥体神经元兴奋性增加有关,而与dCA1脑区似乎关系不大。

Objective:To explore the changes in the excitatory/inhibitory(E/I)balance of pyramidal neurons in prefrontal cortex and hippocampus in mice with anxiety disorder induced by chronic unpredictable mild stress(CUMS).Methods:Twenty-four C57/BL6 male mice were randomly divided into control group(CTRL)and model group(CUMS),with 12 mice in each group.The mice in CUMS group were subjected to 21 days of stress,including restraint for 1 h,reversed day/night cycle for 24 h,forced warm water bath for 5 min,water/food deprivation for 24 h,housing in wet sawdust for 18 h,shaking the cage for 30 min,noise for 1 h,and social stress for 10 min.CTRL group mice were fed normally.Anxiety-related behavioral tests and whole-cell recording tests were performed after modeling.Results:Compared with CTRL group,the time of spent in the central arena of CUMS group was reduced significantly in open field test(P<0.01),the time and number of entering the open arms were decreased significantly in elevated plus maze test(P<0.01),and the time of staying in the closed arms was increased significantly in CUMS group(P<0.01).The sEPSC frequency,capacitance and E/I ratio of dlPFC,mPFC and vCA1 pyramidal neurons of mice in CUMS group were increased significantly(P<0.01),while sEPSC amplitude,sIPSC frequency,amplitude and capacitance were not significantly changed(P>0.05).The frequency,amplitude,capacitance and E/I ratio of sEPSC and sIPSC of dCA1 pyramidal neurons were not significantly changed(P>0.05).Conclusion:The anxiety-like behavior of CUMS-induced mice may be the result of the participation of multiple brain regions,which is mainly related to the increase of the excitability of pyramidal neurons in dlPFC,mPFC and vCA1 brain regions,but seems to have little relationship with dCA1 brain regions.