2. Academic Validation
  3. A small population of stress-responsive neurons in the hypothalamus-habenula circuit mediates development of depression-like behavior in mice

A small population of stress-responsive neurons in the hypothalamus-habenula circuit mediates development of depression-like behavior in mice

  • Neuron. 2024 Oct 3:S0896-6273(24)00660-3. doi: 10.1016/j.neuron.2024.09.012.
Zhiwei Zheng 1,  Yiqin Liu 1,  Ruiqi Mu 2,  Xiaonan Guo 2,  Yirong Feng 2,  Chen Guo 2,  Liang Yang 2,  Wenxi Qiu 2,  Qi Zhang 3,  Wei Yang 4,  Zhaoqi Dong 5,  Shuang Qiu 6,  Yiyan Dong 7,  Yihui Cui 8
Affiliations

Affiliations

  • 1 Department of Psychiatry of Sir Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Neurology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310058, China.
  • 2 Department of Psychiatry of Sir Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310058, China.
  • 3 Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Psychology and Cognitive Science, East China Normal University, Shanghai 200062, China.
  • 4 Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 5 Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
  • 6 NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310058, China.
  • 7 Department of Psychiatry of Sir Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Neurology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310058, China. Electronic address: yiyandong@zju.edu.cn.
  • 8 Department of Psychiatry of Sir Run Shaw Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Neurology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou 310058, China. Electronic address: yihuicui@zju.edu.cn.
PMID: 39389052 DOI: 10.1016/j.neuron.2024.09.012
Abstract

Accumulating evidence has shown that various brain functions are associated with experience-activated neuronal ensembles. However, whether such neuronal ensembles are engaged in the pathogenesis of stress-induced depression remains elusive. Utilizing activity-dependent viral strategies in mice, we identified a small population of stress-responsive neurons, primarily located in the middle part of the lateral hypothalamus (mLH) and the medial part of the lateral habenula (LHbM). These neurons serve as "starter cells" to transmit stress-related information and mediate the development of depression-like behaviors during chronic stress. Starter cells in the mLH and LHbM form dominant connections, which are selectively potentiated by chronic stress. Silencing these connections during chronic stress prevents the development of depression-like behaviors, whereas activating these connections directly elicits depression-like behaviors without stress experience. Collectively, our findings dissect a core functional unit within the LH-LHb circuit that mediates the development of depression-like behaviors in mice.

Keywords

activity-dependent labeling; depression-like behaviors; functional heterogeneity; lateral habenula; lateral hypothalamus; stress-responsive neurons; “starter” cells of stress.

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