A parabrachial to hypothalamic pathway mediates defensive behavior

Fan Wang; Yuge Chen; Yuxin Lin; Xuze Wang; Kaiyuan Li; Yong Han; Jintao Wu; Xingyi Shi; Zhenggang Zhu; Chaoying Long; Xiaojun Hu; Shumin Duan; Zhihua Gao

doi:10.7554/eLife.85450

eLife (Mar 2023)

A parabrachial to hypothalamic pathway mediates defensive behavior

Fan Wang,
Yuge Chen,
Yuxin Lin,
Xuze Wang,
Kaiyuan Li,
Yong Han,
Jintao Wu,
Xingyi Shi,
Zhenggang Zhu,
Chaoying Long,
Xiaojun Hu,
Shumin Duan,
Zhihua Gao

Affiliations

Fan Wang: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Yuge Chen: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Yuxin Lin: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Xuze Wang: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Kaiyuan Li: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Yong Han: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Jintao Wu: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Xingyi Shi: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Zhenggang Zhu: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Chaoying Long: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China
Xiaojun Hu: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China
Shumin Duan: Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China; Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; The Institute of Brain and Cognitive Sciences, Zhejiang University City College, Hangzhou, China; Chuanqi Research and Development Center of Zhejiang University, Hangzhou, China
Zhihua Gao: ORCiD; Department of Neurobiology and Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, MOE Frontier Science Center for Brain Science and Brain-machine Integration, State Key Labotatory of Brain-machine intelligence, Zhejiang University, Hangzhou, China; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, China

DOI: https://doi.org/10.7554/eLife.85450
Journal volume & issue: Vol. 12

Abstract

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Defensive behaviors are critical for animal’s survival. Both the paraventricular nucleus of the hypothalamus (PVN) and the parabrachial nucleus (PBN) have been shown to be involved in defensive behaviors. However, whether there are direct connections between them to mediate defensive behaviors remains unclear. Here, by retrograde and anterograde tracing, we uncover that cholecystokinin (CCK)-expressing neurons in the lateral PBN (LPBCCK) directly project to the PVN. By in vivo fiber photometry recording, we find that LPBCCK neurons actively respond to various threat stimuli. Selective photoactivation of LPBCCK neurons promotes aversion and defensive behaviors. Conversely, photoinhibition of LPBCCK neurons attenuates rat or looming stimuli-induced flight responses. Optogenetic activation of LPBCCK axon terminals within the PVN or PVN glutamatergic neurons promotes defensive behaviors. Whereas chemogenetic and pharmacological inhibition of local PVN neurons prevent LPBCCK-PVN pathway activation-driven flight responses. These data suggest that LPBCCK neurons recruit downstream PVN neurons to actively engage in flight responses. Our study identifies a previously unrecognized role for the LPBCCK-PVN pathway in controlling defensive behaviors.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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