1. Neuroscience

Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice

  1. Chang-Rui Chen  Is a corresponding author
  2. Yu-Heng Zhong
  3. Shan Jiang
  4. Wei Xu
  5. Lei Xiao
  6. Zan Wang
  7. Wei-Min Qu  Is a corresponding author
  8. Zhi-Li Huang  Is a corresponding author
  1. Fudan University, China
  2. The First hospital of Jilin University, China
https://doi.org/10.7554/eLife.69909
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Cite this article
  1. Chang-Rui Chen
  2. Yu-Heng Zhong
  3. Shan Jiang
  4. Wei Xu
  5. Lei Xiao
  6. Zan Wang
  7. Wei-Min Qu
  8. Zhi-Li Huang
(2021)
Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
eLife 10:e69909.
https://doi.org/10.7554/eLife.69909
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Abstract

Hypersomnolence disorder (HD) is characterized by excessive sleep, which is a common sequela following stroke, infection or tumorigenesis. HD is traditionally thought to be associated with lesions of wake-promoting nuclei. However, lesions of a single wake-promoting nucleus, or even two simultaneously, did not exert serious HD. Therefore, the specific nucleus and neural circuitry for HD remain unknown. Here, we observed that the paraventricular nucleus of the hypothalamus (PVH) exhibited higher c-fos expression during the active period (23:00) than during the inactive period (11:00) in mice. Therefore, we speculated that the PVH, in which most neurons are glutamatergic, may represent one of the key arousal-controlling centers. By using vesicular glutamate transporter 2 (vglut2Cre) mice together with fiber photometry, multichannel electrophysiological recordings, and genetic approaches, we found that PVHvglut2 neurons were most active during wakefulness. Chemogenetic activation of PVHvglut2 neurons induced wakefulness for 9 h, and photostimulation of PVHvglut2→parabrachial complex/ventral lateral septum circuits immediately drove transitions from sleep to wakefulness. Moreover, lesioning or chemogenetic inhibition of PVHvglut2 neurons dramatically decreased wakefulness. These results indicate that the PVH is critical for arousal promotion and maintenance.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided at DRYAD (DOI: https://doi.org/10.5061/dryad.bg79cnpb6, https://doi.org/10.5061/dryad.x3ffbg7jw, https://doi.org/10.5061/dryad.r4xgxd2db)

The following data sets were generated

Article and author information

Author details

  1. Chang-Rui Chen

    Fudan University, Shanghai, China
    For correspondence
    changruichen@163.com
    Competing interests
    The authors declare that no competing interests exist.

  2. Yu-Heng Zhong

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Shan Jiang

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Wei Xu

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Lei Xiao

    Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1640-9690

  6. Zan Wang

    The First hospital of Jilin University, Changchun, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Wei-Min Qu

    Fudan University, Shanghai, China
    For correspondence
    quweimin@fudan.edu.cn
    Competing interests
    The authors declare that no competing interests exist.

  8. Zhi-Li Huang

    Fudan University, Shanghai, China
    For correspondence
    huangzl@fudan.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9359-1150

Funding

National Natural Science Foundation of China (81671317)

  • Zhi-Li Huang

National Natural Science Foundation of China (31530035)

  • Chang-Rui Chen

National Natural Science Foundation of China (81420108015)

  • Zhi-Li Huang

National Natural Science Foundation of China (31671099)

  • Zhi-Li Huang

National Natural Science Foundation of China (31871072)

  • Zhi-Li Huang

National Natural Science Foundation of China (31571103)

  • Chang-Rui Chen

National Natural Science Foundation of China (81701305)

  • Zhi-Li Huang

National Natural Science Foundation of China (81970727)

  • Lei Xiao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were approved by the Medical Experimental Animal Administrative Committee of Shanghai. All experimental procedures involving animals were approved by the Animal Experiment and Use Committee of Fudan University (20150119 - 067).

Copyright

© 2021, Chen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Chang-Rui Chen
  2. Yu-Heng Zhong
  3. Shan Jiang
  4. Wei Xu
  5. Lei Xiao
  6. Zan Wang
  7. Wei-Min Qu
  8. Zhi-Li Huang
(2021)
Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
eLife 10:e69909.
https://doi.org/10.7554/eLife.69909

Share this article

https://doi.org/10.7554/eLife.69909

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