A molecularly defined brain circuit module for regulating panic-like defensive state

Miao Zhao, Li Zhang, Zhenhua Chen, Shuangfeng Zhang, Xinyu Cheng, Meizhu Huang, Xiating Li, Huating Gu, Xuyan Guan, Dandan Geng, Yaning Li, Yiheng Tu, Zhiyong Xie, Fan Zhang, Huijie Ma, Xiaoming Li, Dapeng Li (), Qing-Feng Wu () and Peng Cao ()
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Miao Zhao: National Institute of Biological Sciences
Li Zhang: National Institute of Biological Sciences
Zhenhua Chen: Chinese Academy of Sciences
Shuangfeng Zhang: National Institute of Biological Sciences
Xinyu Cheng: National Institute of Biological Sciences
Meizhu Huang: National Institute of Biological Sciences
Xiating Li: Capital Medical University
Huating Gu: National Institute of Biological Sciences
Xuyan Guan: National Institute of Biological Sciences
Dandan Geng: Hebei Medical University
Yaning Li: Hebei Medical University
Yiheng Tu: Chinese Academy of Sciences
Zhiyong Xie: Fudan University
Fan Zhang: Hebei Medical University
Huijie Ma: Hebei Medical University
Xiaoming Li: Zhejiang University School of Medicine
Dapeng Li: Capital Medical University
Qing-Feng Wu: Chinese Academy of Sciences
Peng Cao: National Institute of Biological Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Panic is an episode of strong defensive state, characterized by intense fear and severe physical symptoms such as elevated cardiorespiratory activities. How the brain generates panic state remains poorly understood. Here, we developed a robot-based experimental paradigm to evoke panic-like defensive state in mice. When stimulated by the robot, mice exhibited jumping escapes and elevated cardiorespiratory activities. With this paradigm, we identified Cbln2-expressing (Cbln2+) neurons in the posterior hypothalamic nucleus (PHN) as a key neuronal population essential for the induction of panic-like defensive state. Activation of Cbln2+ PHN neurons induced behavioral and physical symptoms of panic-like defensive state. These neurons were strongly activated by noxious mechanical stimuli and encode jumping escape vigor. They were synaptically innervated by anxiety-associated brain areas and provoked panic-like defensive state via their projection to the periaqueductal gray. Together, our results reveal a molecularly defined circuit module that regulates the panic-like defensive state in mice.

Date: 2025
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DOI: 10.1038/s41467-025-60529-3

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