An entorhinal-visual cortical circuit regulates depression-like behaviors

作者全名："Lu, Jian; Zhang, Zhouzhou; Yin, Xinxin; Tang, Yingjun; Ji, Runan; Chen, Han; Guang, Yu; Gong, Xue; He, Yong; Zhou, Wei; Wang, Haiyang; Cheng, Ke; Wang, Yue; Chen, Xiaowei; Xie, Peng; Guo, Zengcai, V"

作者地址："[Lu, Jian; Gong, Xue; He, Yong; Zhou, Wei; Wang, Haiyang; Cheng, Ke; Wang, Yue; Xie, Peng] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Lu, Jian; Gong, Xue; He, Yong; Zhou, Wei; Wang, Haiyang; Cheng, Ke; Wang, Yue; Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Lu, Jian; Zhang, Zhouzhou; Yin, Xinxin; Tang, Yingjun; Ji, Runan; Chen, Han; Guo, Zengcai, V] Tsinghua Univ, Sch Med, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China; [Lu, Jian; Zhang, Zhouzhou; Yin, Xinxin; Tang, Yingjun; Ji, Runan; Chen, Han; Guo, Zengcai, V] Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China; [Guang, Yu] Shenzhen Univ, Dept Gynecol, Affiliated Hosp 1, Peoples Hosp Shenzhen 2, Shenzhen 518028, Peoples R China; [Guang, Yu] Dapeng Matern & Child Healthcare Hosp, Shenzhen 518028, Peoples R China; [Chen, Xiaowei] Third Mil Med Univ, Brain Res Ctr, Chongqing 400038, Peoples R China; [Chen, Xiaowei] Third Mil Med Univ, State Key Lab Trauma Burns & Combined Injury, Chongqing 400038, Peoples R China"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Xie, P (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Guo, ZCV (通讯作者)，Tsinghua Univ, Sch Med, IDG McGovern Inst Brain Res, Beijing 100084, Peoples R China.; Guo, ZCV (通讯作者)，Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China."

来源：MOLECULAR PSYCHIATRY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000779714800003

JCR分区：Q1

影响因子：11

年份：2022

卷号：　

期号：　

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结束页：　

文献类型：Article; Early Access

关键词：　

摘要："Major depressive disorder is viewed as a 'circuitopathy'. The hippocampal-entorhinal network plays a pivotal role in regulation of depression, and its main sensory output, the visual cortex, is a promising target for stimulation therapy of depression. However, whether the entorhinal-visual cortical pathway mediates depression and the potential mechanism remains unknown. Here we report a cortical circuit linking entorhinal cortex layer Va neurons to the medial portion of secondary visual cortex (Ent -> V2M) that bidirectionally regulates depression-like behaviors in mice. Analyses of brain-wide projections of Ent Va neurons and two-color retrograde tracing indicated that Ent Va -> V2M projection neurons represented a unique population of neurons in Ent Va. Immunostaining of c-Fos revealed that activity in Ent Va neurons was decreased in mice under chronic social defeat stress (CSDS). Both chemogenetic inactivation of Ent -> V2M projection neurons and optogenetic inactivation of the projection terminals induced social deficiency, anxiety- and despair-related behaviors in healthy mice. Chemogenetic inactivation of Ent -> V2M projection neurons also aggravated these depression-like behaviors in CSDS-resilient mice. Optogenetic activation of Ent -> V2M projection terminals rapidly ameliorated depression-like phenotypes. Optical recording using fiber photometry indicated that elevated neural activity in Ent -> V2M projection terminals promoted antidepressant-like behaviors. Thus, the Ent -> V2M circuit plays a crucial role in regulation of depression-like behaviors, and can function as a potential target for treating major depressive disorder."

基金机构：National Natural Science Foundation of China [32021002]; National Key R&D Program of China [2017YFA0505700]

基金资助正文："We thank Hailan Hu, Cheng Zhan and Ji Hu for comments on the manuscript. We also thank Pengfei Wei, Yu Wang, Yan Huo, Tianyi Huang, Fan Di, Hongjiang Yang, Yuexin Yang and Xiao Yao for generous assistance in the experiments of animal breeding, electrophysiological recording and morphology; the Cell Biology Facility, Center of Biomedical Analysis at Tsinghua University for imaging of brain sections; the Animal Core Facility at Tsinghua University for maintaining the mouse lines. This work was supported by the National Natural Science Foundation of China (32021002) to ZVG and the National Key R&D Program of China (2017YFA0505700) to PX."