丘脑连接核对NREM睡眠期内侧前额叶皮层纺锤波的影响  

Effect of thalamic nucleus reuniens on spindle waves in the medial prefrontal cortex during non-rapid eye movement sleep

作　　者：张磊[1] 陆敏敏 张小龙 何超[1] 肖琴[1] ZHANG Lei;LU Minmin;ZHANG Xiaolong;HE Chao;XIAO Qin(Department of Physiology,College of Basic Medical Sciences,Army Medical University(Third Military Medical University),Chongqing,China)

机构地区：[1]陆军军医大学(第三军医大学)基础医学院生理学教研室,重庆

出　　处：《陆军军医大学学报》2025年第4期298-306,共9页Journal of Army Medical University

基　　金：重庆市杰出青年科学基金项目(CSTB2022NSCQ-JQX0019)。

摘　　要：目的探索丘脑连接核(thalamic nucleus reuniens,RE)在非快速眼动(non-rapid eye movement,NREM)睡眠期间对内侧前额叶皮层(medial prefrontal cortex,mPFC)纺锤波以及神经元活动的影响。方法将13只野生型C57BL/6J雄性小鼠(8~12周龄,体质量22~28 g)随机分为实验组(n=7)和对照组(n=6)。采用光遗传抑制技术结合多通道记录技术,在NREM睡眠期间用特异性黄光抑制RE投射到mPFC的神经元末梢20 s,两次光刺激间隔大于5 min。根据神经元的波宽参数和放电频率,鉴定神经元类型和分布情况,并分析抑制后mPFC中纺锤波活动的变化以及中间神经元和锥体神经元的放电变化。结果形态学数据验证了RE发出的神经纤维密集的投射到mPFC,且主要分布在深层。与光刺激前相比,实验组小鼠在光刺激期间mPFC的纺锤波活动受到明显影响,主要表现在纺锤波的发生频率降低、中心频率降低以及峰-峰值降低(P<0.05),对纺锤波时长、循环个数、对称性及能量值均无影响,同时,在对照组小鼠中的纺锤波指标没有明显变化。小鼠mPFC的中间神经元占比为21.9%,锥体神经元占比为78.1%。光刺激期间实验组中间神经元的放电频率明显下降(P<0.05),锥体神经元的放电频率没有明显变化,而对照组小鼠的中间神经元及锥体神经元的放电活动均不受影响。结论在NREM睡眠期间,RE输入可能通过激活中间神经元,从而参与mPFC的纺锤波网络振荡的发生。Objective To determine the effect of thalamic nucleus reuniens(RE)on sleep spindles and neuronal activity in the medial prefrontal cortex(mPFC)during non-rapid eye movement(NREM)sleep.Methods Thirteen wild-type C57BL/6 male mice(8~12 weeks old,weighing 22~28 g)were randomly divided into an experimental group(n=7)and a control group(n=6).Optogenetic inhibition combined with multi-channel recording technology was used to specifically inhibit RE projections to mPFC during NREM sleep with yellow light for 20 s,in a 5-min interval between 2 times of light stimuli.The types and distribution of neurons were identified based on the waveform width and firing frequency of neurons.The changes in spindle activity in the mPFC following inhibition,as well as in firing of interneurons and pyramidal neurons were analyzed.Results Morphological data confirmed that neural fibers originating from the RE densely projected to the mPFC,primarily distributed in the deep layers.In the experimental group,light stimulation significantly affected the spindle activity in the mPFC when compared with the period before light stimulation,mainly manifested as a decrease in spindle rate,central frequency,and peak-to-peak amplitude(P<0.05).However,no impacts on spindle duration,number of cycles,symmetry,and power were observed.Meanwhile,there were no significant changes in the spindle activity of the control group.The proportion of interneurons in the mPFC area was 21.9%,while pyramidal neurons accounted for 78.1%.The firing rates of interneurons in the experimental group decreased significantly during light stimulation(P<0.05),whereas there was no significant change in the firing rates of pyramidal neurons.In addition,the firing activities of both interneurons and pyramidal neurons in the control group remained unaffected.Conclusion During NREM sleep,RE inputs may participate in the generation of sleep spindles network oscillations in the mPFC by activating interneurons.

关 键 词：丘脑连接核 非快速眼动 内侧前额叶皮层 光遗传抑制 纺锤波 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R338.2[医药卫生—基础医学] R338.6