Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
- Fudan University, China
- The First hospital of Jilin University, China
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)
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EEG/EMG, Photometry and Electrophysiological dataDryad Digital Repository, doi:10.5061/dryad.bg79cnpb6.
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electrophysiological dataDryad Digital Repository, doi:10.5061/dryad.x3ffbg7jw.
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CRF and CORT, heart rate, temperatureDryad Digital Repository, doi: 10.5061/dryad.r4xgxd2db.
Article and author information
Author details
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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Dysfunctions of the paraventricular hypothalamic nucleus induce hypersomnia in mice
eLife 10:e69909.
https://doi.org/10.7554/eLife.69909
