PUBLICATION
The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a Cooperative Mechanism
- Authors
- 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.
- ID
- ZDB-PUB-180921-11
- 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
-
- Anesthetics, Intravenous/pharmacology*
- Animals
- Dopamine beta-Hydroxylase/genetics
- Etomidate/pharmacology*
- GABAergic Neurons/drug effects
- GABAergic Neurons/metabolism
- GABAergic Neurons/physiology
- Locomotion
- Locus Coeruleus/drug effects*
- Locus Coeruleus/metabolism
- Locus Coeruleus/physiology
- Norepinephrine/metabolism
- Propofol/pharmacology*
- Synaptic Potentials
- Zebrafish
- Zebrafish Proteins/genetics
- PubMed
- 30231998 Full text @ Cell Rep.
Citation
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. (2018) The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a Cooperative Mechanism. Cell Reports. 24:3146-3155.e3.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping