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

Cell Reports
Wen-Jie DUJiu-lin Du

Abstract

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.

Citations

Jul 18, 2019·Critical Reviews in Toxicology·Luís FélixLuís Antunes
Oct 2, 2019·Current Neuropharmacology·Angeles Edith Espino-SaldañaAtaúlfo Martínez-Torres
Mar 20, 2020·BioMed Research International·Song CaoTian Yu
Jun 12, 2020·Physiological Reviews·Rohini Kuner, Thomas Kuner
Aug 17, 2021·Environmental Science & Technology·Sarah KönemannColette Vom Berg

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