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Peer-reviewedCC BY-NCScience Advances

Neural circuitry mediating hypercapnia-induced microarousal and impaired sleep depth

  • Chen Yang
  • Wen-Xuan Tang
  • Wen-Xu Wang
  • Xiao-Long Lv
  • Xin-Yi Wang
  • Dan-Ni He
  • Hao Wen
  • Jia-hui Guo
  • Jin-Xuan Zhou
  • Jian Guan1,2
  • Jing Cang3
  • Shi-Bin Li
  1. 1Department of Otolaryngology Head and Neck Surgery, Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China.
  2. 2Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai 200233, China.
  3. 3Department of Pain Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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Abstract

Sleep disruption in obstructive sleep apnea syndrome is characterized by frequent microarousals and reduced sleep depth, yet the underlying mechanisms remain unclear. Here, we show that intermittent hypercapnic air (HA) induces time-locked microarousals, fragments sleep, reduces non-rapid eye movement (NREM) sleep depth, and diminishes rapid eye movement (REM) sleep. HA exposure activates glutamatergic neurons in the nucleus tract solitary (NTSVglut2), and their optogenetic or chemogenetic activation is sufficient to trigger arousal and impair sleep. Projection-specific activation reveals that NTSVglut2 projections to the paraventricular nucleus (PVN), parabrachial nucleus (PB), paraventricular thalamus, and locus coeruleus (LC) promote arousal, whereas projections to the PB and LC additionally reduce NREM sleep depth. Inhibition of NTSVglut2 projection to the PVN significantly postpones HA-induced arousal. NTSVglut2 terminals monosynaptically activate corticotropin-releasing hormone neurons in the PVN (PVNCRH), and inhibition of PVNCRH neurons or knockdown of Slc17a6 (encoding Vglut2), but not Crh, delays hypercapnia-induced arousal. These findings identify neural circuits underlying hypercapnia-induced microarousal and reduced sleep depth.

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Cite

BibTeXRIS
BibTeX
@article{yang2026neural,
  title = {{Neural circuitry mediating hypercapnia-induced microarousal and impaired sleep depth}},
  author = {Chen Yang and Wen-Xuan Tang and Wen-Xu Wang and Xiao-Long Lv and Xin-Yi Wang and Dan-Ni He and Hao Wen and Jia-hui Guo and Jin-Xuan Zhou and Jian Guan and Jing Cang and Shi-Bin Li},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aei1892},
  url = {https://www.science.org/doi/10.1126/sciadv.aei1892},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Neural circuitry mediating hypercapnia-induced microarousal and impaired sleep depth
AU  - Chen Yang
AU  - Wen-Xuan Tang
AU  - Wen-Xu Wang
AU  - Xiao-Long Lv
AU  - Xin-Yi Wang
AU  - Dan-Ni He
AU  - Hao Wen
AU  - Jia-hui Guo
AU  - Jin-Xuan Zhou
AU  - Jian Guan
AU  - Jing Cang
AU  - Shi-Bin Li
PY  - 2026
DA  - 2026/10/23
JO  - Science Advances
DO  - 10.1126/sciadv.aei1892
UR  - https://www.science.org/doi/10.1126/sciadv.aei1892
AB  - Sleep disruption in obstructive sleep apnea syndrome is characterized by frequent microarousals and reduced sleep depth, yet the underlying mechanisms remain unclear. Here, we show that intermittent hypercapnic air (HA) induces time-locked microarousals, fragments sleep, reduces non-rapid eye movement (NREM) sleep depth, and diminishes rapid eye movement (REM) sleep. HA exposure activates glutamatergic neurons in the nucleus tract solitary (NTSVglut2), and their optogenetic or chemogenetic activation is sufficient to trigger arousal and impair sleep. Projection-specific activation reveals that NTSVglut2 projections to the paraventricular nucleus (PVN), parabrachial nucleus (PB), paraventricular thalamus, and locus coeruleus (LC) promote arousal, whereas projections to the PB and LC additionally reduce NREM sleep depth. Inhibition of NTSVglut2 projection to the PVN significantly postpones HA-induced arousal. NTSVglut2 terminals monosynaptically activate corticotropin-releasing hormone neurons in the PVN (PVNCRH), and inhibition of PVNCRH neurons or knockdown of Slc17a6 (encoding Vglut2), but not Crh, delays hypercapnia-induced arousal. These findings identify neural circuits underlying hypercapnia-induced microarousal and reduced sleep depth.
SN  - 2375-2548
ER  -