Anxiety-related cell-type-specific neural circuits in the anterior-dorsal bed nucleus of the stria terminalis  

前背侧终纹床核中与焦虑相关的细胞类型特异性神经环路图谱的研究

作　　者：Xinxin Wang Yongsheng Zhang Xu Wang Jiaqi Dai Ruifang Hua Shaoqun Zeng Haohong Li 王鑫鑫;张勇升;王旭;代家起;化瑞芳;曾绍群;李浩洪(Britton Chance Center for Biomedical Photonics,Wuhan National Laboratory for Optoelectronics,Huazhong University of Science and Technology,Wuhan 430074,China;Ministry of Education Key Laboratory for Biomedical Photonics,Collaborative Innovation Center for Biomedical Engineering,School of Engineering Sciences,Huazhong University of Science and Technology,Wuhan 430074,China)

机构地区：[1]Britton Chance Center for Biomedical Photonics,Wuhan National Laboratory for Optoelectronics,Huazhong University of Science and Technology,Wuhan 430074,China [2]Ministry of Education Key Laboratory for Biomedical Photonics,Collaborative Innovation Center for Biomedical Engineering,School of Engineering Sciences,Huazhong University of Science and Technology,Wuhan 430074,China

出　　处：《Science Bulletin》2020年第14期1203-1216,M0004,共15页科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31671105);Science Fund for Creative Research Group of China(61721092),“National Basic Research Program of China”(973 program 2015CB755603);Director Fund of the Wuhan National Laboratory for Optoelectronics and partly supported by the open funds of the State Key Laboratory of Medical Neurobiology,Fudan University.

摘　　要：The bed nucleus of the stria terminalis(BNST) plays a critical role in regulating anxiety, yet the involved specific cell types and their connections functioning in anxiety-related behaviors remains elusive. Here we identified two cell subpopulations—corticotropin-releasing hormone-positive(CRH+) and protein kinase C-δ-positive(PKC-δ+) neurons—each displayed discrete emotionally valenced behaviors in the anterior-dorsal BNST(ad BNST). Using whole-cell patch-clamp recordings and virus-assisted circuit tracing techniques, we delineated the local and long-range connectivity networks in a cell-type-specific manner. The results show that the CRH+ and PKC-δ+ neurons received inputs from similar brain regions and exhibited significant differences in the downstream projection density. In addition, in vivo calcium imaging as well as gain-and loss-of-function studies characterized the physiological response properties and the functional heterogeneities in modulating anxiety, further suggesting the similarity and individuality between the two ad BNST cell types. These results provide novel insights into the circuit architecture of ad BNST neurons underlying the functionally specific neural pathways that relate to anxiety disorders.焦虑是生物个体面临外界环境潜在威胁时的本能反应.既往研究表明终纹床核(the bed nucleus of the stria terminalis, BNST)在调节焦虑过程中起着重要作用,但其中与焦虑行为相关的神经环路构筑和功能尚未可知.本研究在前背侧终纹床核(anterior-dorsal BNST, ad BNST)中发现两类独立分布的细胞群体,分别特异性表达促肾上腺皮质激素释放激素(corticotropin-releasing hormone, CRH)和蛋白激酶C-δ(protein kinase C-δ, PKC-δ)分子.利用神经环路示踪、全细胞膜片钳、在体神经元钙离子成像以及化学遗传学手段,本文阐明了ad BNST的CRH与PKC-δ阳性神经元的局部和长距离的神经环路连接特点及其对小鼠焦虑行为产生的不同调控作用.研究结果表明, CRH与PKC-δ神经元接收相似的上游脑区神经投射,并在部分下游脑区的投射密度中表现出显著性差异.该结果提示,二者可能参与到不同的焦虑行为调控中.进一步的功能研究结果发现,特异性地操纵CRH和PKC-δ阳性神经元能够分别产生致焦虑和抗焦虑作用.本研究揭示了ad BNST脑区CRH与PKC-δ神经元的功能异质性,为后续调控焦虑的神经环路机制的研究提供了坚实的基础.

关 键 词：Anterior-dorsal BNST CRH PKC-δ ANXIETY 

分 类 号：R749.72[医药卫生—神经病学与精神病学]