免疫抑制
外围设备
失眠症
神经科学
生物
内科学
医学
生物信息学
药理学
免疫学
作者
Shi‐Bin Li,Jeremy C. Borniger,Hiroshi Yamaguchi,Julien Hédou,Brice Gaudillière,Luı́s de Lecea
出处
期刊:Science Advances
[American Association for the Advancement of Science]
日期:2020-09-09
卷期号:6 (37)
被引量:110
标识
DOI:10.1126/sciadv.abc2590
摘要
The neural substrates of insomnia/hyperarousal induced by stress remain unknown. Here, we show that restraint stress leads to hyperarousal associated with strong activation of corticotropin-releasing hormone neurons in the paraventricular nucleus of hypothalamus (CRHPVN) and hypocretin neurons in the lateral hypothalamus (HcrtLH). CRHPVN neurons directly innervate HcrtLH neurons, and optogenetic stimulation of LH-projecting CRHPVN neurons elicits hyperarousal. CRISPR-Cas9-mediated knockdown of the crh gene in CRHPVN neurons abolishes hyperarousal induced by stimulating LH-projecting CRHPVN neurons. Genetic ablation of Hcrt neurons or crh gene knockdown significantly counteracts restraint stress-induced hyperarousal. Single-cell mass cytometry by time of flight (CyTOF) revealed extensive changes to immune cell distribution and functional responses in peripheral blood during hyperarousal upon optogenetic stimulation of CRHPVN neurons simulating stress-induced insomnia. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRHPVN circuitry.
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