The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a Cooperative Mechanism

• Main Authors: Wen-jie Du, Rong-wei Zhang, Jia Li, Bai-bing Zhang, Xiao-lan Peng, Song Cao, Jie Yuan, Cheng-dong Yuan, Tian Yu, Jiu-lin Du
• Format: Article
• Language: English
• Published: Elsevier 2018-09-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124718313329

Summary: How general anesthesia causes loss of consciousness has been a mystery for decades. It is generally thought that arousal-related brain nuclei, including the locus coeruleus (LC), are involved. Here, by monitoring locomotion behaviors and neural activities, we developed a larval zebrafish model for studying general anesthesia induced by propofol and etomidate, two commonly used intravenous anesthetics. Local lesion of LC neurons via two-photon laser-based ablation or genetic depletion of norepinephrine (NE; a neuromodulator released by LC neurons) via CRISPR/Cas9-based mutation of dopamine-β-hydroxylase (dbh) accelerates induction into and retards emergence from general anesthesia. Mechanistically, in vivo whole-cell recording revealed that both anesthetics suppress LC neurons’ activity through a cooperative mechanism, inhibiting presynaptic excitatory inputs and inducing GABAA receptor-mediated hyperpolarization of these neurons. Thus, our study indicates that the LC-NE system plays a modulatory role in both induction of and emergence from intravenous general anesthesia. : The locus coeruleus (LC)-norepinephrine (NE) system is involved in general anesthesia. Here, Du et al. show that the LC-NE system plays a modulatory role in the induction and emergence of intravenous general anesthesia induced by propofol and etomidate, both of which suppress LC neuronal activities through a cooperative mechanism. Keywords: propofol, etomidate, intravenous general anesthesia, norepinephrine, locus coeruleus, zebrafish