美国纽约州西奈山伊坎医学院Denise J. Cai团队的一项最新研究的研究开发出了杏仁核连接下丘脑前回路，控制应激敏感性。相关论文发表在2026年9月30日出版的《自然》杂志上。

先前的不良经历会增加对后续应激事件的敏感性，但其背后脑回路中的因果性变化仍知之甚少。在此，研究人员利用无偏全脑活动图谱来鉴定因先前不良经历而发生功能性重塑、从而促进应激敏感性升高的回路。下丘脑前核（AHN）——一个迄今为止在应激背景下很少受到关注的区域——在先前受过应激的小鼠中表现出应激反应性增强。这伴随着AHN与威胁相关脑网络之间相关性强度的增加。随后，使用体内微型显微镜成像，研究人员发现AHN中的神经元活动随负效价而变化。此外，先前应激放大了效价敏感性AHN神经元的比例，表明AHN中对负效价处理的增强可能驱动应激敏感性升高。为AHN在负效价和应激敏感性中的作用提供因果支持，抑制AHN神经元减弱了应激反应，而兴奋其活动则促进了应激反应。最后，研究人员发现投射到AHN的杏仁核神经元追踪负效价，并且沉默杏仁核到AHN的输入消除了敏化的应激反应。这些发现确定了AHN在调控来自杏仁核的负效价信号中的关键作用，并突出了一条提高对应激事件敏感性的新通路。

附：英文原文

Title: An amygdala to anterior hypothalamic circuit gates stress sensitivity

Author: Pennington, Zachary T., LaBanca, Alexa R., Mahmud, Afra N., Abdel-Raheim, Shereen D., Bacon, Madeline E., Sompolpong, Patlapa, Ko, BumJin, Baggetta, Austin M., Zaki, Yosif, Feng, Yu, Dong, Zhe, Smith, Alexander C. W., Shuman, Tristan, Kenny, Paul J., Cai, Denise J.

Issue&Volume: 2026-09-30

Abstract: Previous adversity increases sensitivity to subsequent stressful events1,2,3,4,5,6,7,8, but the causal underlying changes in brain circuitry are poorly understood. Here we harnessed unbiased whole-brain activity mapping to identify circuits that are functionally remodelled by previous adversity to promote heightened stress sensitivity. The anterior hypothalamic nucleus (AHN)—a region that has received little attention until now in the context of stress—displayed heightened stress reactivity in previously stressed mice. This was accompanied by increased correlational strength between the AHN and a threat-related brain network. Using in vivo Miniscope imaging, we then found that neuronal activity in the AHN scales with negative valence. Moreover, previous stress amplified the proportion of valence-sensitive AHN neurons, indicating inflated processing of negative valence in the AHN might drive heightened stress sensitivity. Providing causal support for the role of AHN in negative valence and stress sensitivity, inhibiting AHN neurons blunted, and exciting their activity promoted, stress responses. Finally, amygdala neurons that project to the AHN were found to track negative valence, and silencing amygdala inputs to the AHN abolished sensitized stress responses. These findings define a key role of the AHN in regulating negative valence signals from the amygdala and highlight a new pathway that heightens sensitivity to stressful events.

DOI: 10.1038/s41586-026-11075-5

Source: https://www.nature.com/articles/s41586-026-11075-5