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Lateral Habenula Neurons Signal Cold Aversion and Participate in Cold Aversion

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Abstract

The aversion to cold is a fundamental motivated behavior that contributes to the body temperature homeostasis. However, the involvement of the lateral habenula (LHb) as a regulatory hub for negative emotions in this physiological process remains uninvestigated. In this study, we demonstrate an elevation in the population activity of LHb neurons following exposure to cold stimuli. Additionally, we establish the necessity of Vglut2-expressing neurons within the LHb for the encoding of cold aversion behaviors. Furthermore, we have elucidated a neural circuit from excitatory neurons of the dorsomedial hypothalamus (DMH) to LHb that plays a crucial role in this progress. Manipulation of the DMH-LHb circuit has a significant impact on cold aversion behavior in mice. It is worth noting that this circuit does not exhibit any noticeable effects on autonomic thermoregulation or depression-like behavior. The identification of these neural mechanisms involved in behavioral thermoregulation provides a promising avenue for future research.

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Funding

This work was supported by the National Natural Science Foundations of China (81971135; 8217070610; 81801303); Natural Science Foundations of Heilongjiang (YQ2020H014); the “Chunhui Plan” of the Ministry of Education (HLJ2019009); Distinguished Young Foundations of the First Affiliated Hospital of Harbin Medical University (HYD2020JQ0014).

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Youzheng Street 23, Nangang District, Harbin, 150001, Heilongjiang Province, People’s Republic of China

    Rui Liu, Huan Xiang, Chunyang Liu, Qiuyi Jiang, Yanchao Liang, Guangzheng Wang & Guang Yang

  2. Institute of Brain Science, Harbin Medical University, Harbin, People’s Republic of China

    Rui Liu, Huan Xiang, Chunyang Liu, Qiuyi Jiang, Yanchao Liang, Guangzheng Wang & Guang Yang

  3. Department of Urology (Heilongjiang Key Laboratory of Scientific Research in Urology), The Fourth Affiliated Hospital of Harbin Medical University, Youzheng Street 23, Nangang District, Harbin, Heilongjiang Province, People’s Republic of China

    Lu Wang

  4. Department of Human Anatomy, Binzhou Medical College, 346 Guanhai Rd, Yantai City, People’s Republic of China

    Yi Sun

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  1. Rui Liu
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  2. Huan Xiang
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Contributions

GY, YS, LW, and RL designed experiments. RL, HX, CL and QJ performed experiments. YL, GW and RL analyzed data. RL, HX, GY and YS wrote the main manuscript text. All authors have reviewed the manuscript.

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Correspondence to Lu Wang, Yi Sun or Guang Yang.

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The authors declare that there are no conflicts of interest.

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All animal procedures were approved by the Institutional Animal Care and Use Committee of Harbin Medical School, and experiments were performed in accordance to the CPCSEA guidelines for ethical use of animals.

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Liu, R., Xiang, H., Liu, C. et al. Lateral Habenula Neurons Signal Cold Aversion and Participate in Cold Aversion. Neurochem Res 49, 771–784 (2024). https://doi.org/10.1007/s11064-023-04076-7

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