Zhao Miao, Zhang Li, Chen Zhenhua, Zhang Shuangfeng, Cheng Xinyu, Huang Meizhu, Li Xiating, Gu Huating, Guan Xuyan, Geng Dandan, Li Yaning, Tu Yiheng, Xie Zhiyong, Zhang Fan, Ma Huijie, Li Xiaoming, Li Dapeng, Wu Qing-Feng, Cao Peng
National Institute of Biological Sciences, Beijing, China.
State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2025 Jul 1;16(1):5523. doi: 10.1038/s41467-025-60529-3.
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.
惊恐是一种强烈的防御状态发作，其特征为强烈恐惧和严重的身体症状，如心肺活动增强。大脑如何产生惊恐状态仍知之甚少。在此，我们开发了一种基于机器人的实验范式，以在小鼠中诱发类似惊恐的防御状态。当受到机器人刺激时，小鼠表现出跳跃逃避和心肺活动增强。利用这种范式，我们确定下丘脑后核（PHN）中表达Cbln2的（Cbln2+）神经元是诱导类似惊恐防御状态所必需的关键神经元群体。激活Cbln2+ PHN神经元会诱发类似惊恐防御状态的行为和身体症状。这些神经元受到有害机械刺激的强烈激活，并编码跳跃逃避的活力。它们接受与焦虑相关脑区的突触支配，并通过投射到导水管周围灰质引发类似惊恐的防御状态。总之，我们的结果揭示了一个分子定义的神经回路模块，该模块调节小鼠的类似惊恐防御状态。
