NE contribution to rebooting unconsciousness caused by midazolam
LeYuan Gu,
WeiHui Shao,
Lu Liu,
Qing Xu,
YuLing Wang,
JiaXuan Gu,
Yue Yang,
ZhuoYue Zhang,
YaXuan Wu,
Yue Shen,
Qian Yu,
XiTing Lian,
HaiXiang Ma,
YuanLi Zhang,
HongHai Zhang
Affiliations
LeYuan Gu
Department of Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
WeiHui Shao
Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Lu Liu
Department of Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China
Qing Xu
Department of Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China
YuLing Wang
Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
JiaXuan Gu
Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
Yue Yang
Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China
ZhuoYue Zhang
Department of Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China
Department of Anesthesiology, Zhejiang University School of Medicine, Hangzhou, China; Department of Anesthesiology, the Fourth Clinical School of Medicine, Zhejiang Chinese Medical University, Hangzhou, China; Department of Anesthesiology, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine, Hangzhou, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.
