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A brainstem circuit amplifies aversion

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机构： [1]National Institute of Biological Sciences (NIBS), Beijing 102206, China [2]Division of Neurobiology, MRC Laboratory of Molecular Biology, Cambridge, UK [3]Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China [4]Chinese Institute for Brain Research (CIBR), Beijing 102206, China [5]HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou 215125, China [6]State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou 570228, China [7]Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing 100053, China [8]Neurodegenerative Laboratory of Ministry of Education of the People’s Republic of China, Beijing 100053, China [9]School of Basic Medical Sciences, Peking University, Beijing 100191, China [10]New Cornerstone Science Laboratory, Shenzhen 518054, China [11]Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing 100005, China [12]Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China

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Dynamic gain control of aversive signals enables adaptive behavioral responses. Although the role of amygdalar circuits in aversive processing is well established, the neural pathway for amplifying aversion remains elusive. Here, we show that the brainstem circuit linking the interpeduncular nucleus (IPN) with the nucleus incertus (NI) amplifies aversion and promotes avoidant behaviors. IPN GABA neurons are activated by aversive stimuli and their predicting cues, with their response intensity closely tracking aversive values. Activating these neurons does not trigger aversive behavior on its own but rather amplifies responses to aversive stimuli, whereas their ablation or inhibition suppresses such responses. Detailed circuit dissection revealed anatomically distinct subgroups within the IPN GABA neuron population, highlighting the NI-projecting subgroup as the modulator of aversiveness related to fear and opioid withdrawal. These findings unveil the IPN-NI circuit as an aversion amplifier and suggest potential targets for interventions against affective disorders and opioid relapse.Copyright © 2024 Elsevier Inc. All rights reserved.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区神经科学

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大类 | 1 区

医学

小类 | 1 区神经科学

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影响因子： 15 最新[2024版] 16.6 最新五年平均 16.2 出版当年[2022版] 18.6 出版当年五年平均 18.688 出版前一年[2021版] 14.7 出版后一年[2023版]

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第一作者机构： [1]National Institute of Biological Sciences (NIBS), Beijing 102206, China [2]Division of Neurobiology, MRC Laboratory of Molecular Biology, Cambridge, UK

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通讯机构： [3]Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China [4]Chinese Institute for Brain Research (CIBR), Beijing 102206, China [10]New Cornerstone Science Laboratory, Shenzhen 518054, China [11]Research Unit of Medical Neurobiology, Chinese Academy of Medical Sciences, Beijing 100005, China [12]Beijing Institute for Brain Research, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 102206, China

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