Input-output specific orchestration of aversive valence in lateral habenula during stress dynamics  

作　　者：Taida HUANG Xiaonan GUO Xiaomin HUANG Chenju YI Yihui CUI Yiyan DONG 

机构地区：[1]Department of Neurology and International Institutes of Medicine,the Fourth Affiliated Hospital,Zhejiang University School of Medicine,Yiwu 322000,China [2]Department of Neurology of Sir Run Run Shaw Hospital and School of Brain Science and Brain Medicine,Zhejiang University School of Medicine,Hangzhou 310058,China [3]NHC and CAMS Key Laboratory of Medical Neurobiology,MOE Frontier Science Center for Brain Science and Brain-Machine Integration,Zhejiang University,Hangzhou 310058,China [4]Research Centre,the Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen 518107,China [5]Guangdong Provincial Key Laboratory of Brain Function and Disease,Guangzhou 510080,China [6]Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research,Shenzhen 518107,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第12期1055-1065,共11页浙江大学学报(英文版)B辑(生物医学与生物技术)

基　　金：supported by the STI2030-Major Projects(No.2022ZD0211700);the National Natural Science Foundation of China(Nos.32371057,31922031,32071017,81971309,32170980,82201707,and 82200562);the Zhejiang Provincial Natural Science Foundation of China(No.LDQ24C090001);the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2023PT310-01);the CAS Youth Interdisciplinary Team(No.JCTD2022-11);the China Postdoctoral Science Foundation(No.BX20230319);the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515020012 and 2021A1515110121);the Science and Technology Planning Project of Guangdong Province(No.2023B1212060018);the Shenzhen Fundamental Research Program(Nos.JCYJ20210324123212035,RCYX20200714114644167,ZDSYS20220606100801003,JCYJ20210324122809025,and JCYJ20230807110315031),China。

摘　　要：Stress has been considered as a major risk factor for depressive disorders,triggering depression onset via inducing persistent dysfunctions in specialized brain regions and neural circuits.Among various regions across the brain,the lateral habenula(LHb)serves as a critical hub for processing aversive information during the dynamic process of stress accumulation,thus having been implicated in the pathogenesis of depression.LHb neurons integrate aversive valence conveyed by distinct upstream inputs,many of which selectively innervate the medial part(LHbM)or lateral part(LHbL)of LHb.LHb subregions also separately assign aversive valence via dissociable projections to the downstream targets in the midbrain which provides feedback loops.Despite these strides,the spatiotemporal dynamics of LHb-centric neural circuits remain elusive during the progression of depression-like state under stress.In this review,we attempt to describe a framework in which LHb orchestrates aversive valence via the input-output specific neuronal architecture.Notably,a physiological form of Hebbian plasticity in LHb under multiple stressors has been unveiled to incubate neuronal hyperactivity in an input-specific manner,which causally encodes chronic stress experience and drives depression onset.Collectively,the recent progress and future efforts in elucidating LHb circuits shed light on early interventions and circuit-specific antidepressant therapies.

关 键 词：Lateral habenula Neural circuits AVERSION Stress dynamics Depression-like state Head-to-head comparison 

分 类 号：R74[医药卫生—神经病学与精神病学]