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ZFIN ID: ZDB-PUB-180921-11
The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a Cooperative Mechanism
Du, W.J., Zhang, R.W., Li, J., Zhang, B.B., Peng, X.L., Cao, S., Yuan, J., Yuan, C.D., Yu, T., Du, J.L.
Date: 2018
Source: Cell Reports   24: 3146-3155.e3 (Journal)
Registered Authors: Bai-Bing, Zhang, Du, Jiu Lin, Jia, Li, Peng, Xiao-Lan, Rong-Wei, Zhang
Keywords: etomidate, intravenous general anesthesia, locus coeruleus, norepinephrine, propofol, zebrafish
MeSH Terms: none
PubMed: 30231998 Full text @ Cell Rep.
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.