下丘脑
清醒
光遗传学
促肾上腺皮质激素释放激素
内科学
内分泌学
基因敲除
免疫系统
神经科学
战斗或逃跑反应
生物
医学
免疫学
基因
脑电图
生物化学
作者
Shi‐Bin Li,Jeremy C. Borniger,Hiroshi Yamaguchi,Julien Hédou,Brice Gaudillière,Luı́s de Lecea
标识
DOI:10.1101/2020.04.29.069393
摘要
Abstract 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 (CRH PVN ) and hypocretin neurons in the lateral hypothalamus (Hcrt LH ). CRH PVN neurons are quiescent during natural sleep-wake transitions but are strongly active under restraint stress. CRISPR-Cas9-mediated knockdown of the crh gene in CRH PVN neurons abolishes hyperarousal elicited by stimulating LH-projecting CRH PVN neurons. Genetic ablation of Hcrt neurons or crh gene knockdown significantly reduces insomnia/hyperarousal induced by restraint stress. Given the association between stress and immune function, we used single-cell mass cytometry by time of flight (CyTOF) to analyze peripheral blood and found extensive changes to immune cell distribution and functional responses during wakefulness upon optogenetic stimulation of CRH PVN neurons. Our findings suggest both central and peripheral systems are synergistically engaged in the response to stress via CRH PVN circuitry.
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