PUBLICATION
Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish
- Authors
- Singh, C., Oikonomou, G., Prober, D.A.
- ID
- ZDB-PUB-150917-6
- Date
- 2015
- Source
- eLIFE 4: e07000 (Journal)
- Registered Authors
- Prober, David
- Keywords
- hypocretin, neuroscience, norepinephrine, sleep, zebrafish
- MeSH Terms
-
- Arousal/drug effects*
- Orexins/metabolism*
- Wakefulness/drug effects*
- Zebrafish/genetics
- Zebrafish/physiology*
- Animals
- Norepinephrine/deficiency
- Norepinephrine/metabolism*
- Autonomic Nervous System Diseases
- Dopamine beta-Hydroxylase/deficiency
- Dopamine beta-Hydroxylase/genetics
- Dopamine beta-Hydroxylase/metabolism
- PubMed
- 26374985 Full text @ Elife
Citation
Singh, C., Oikonomou, G., Prober, D.A. (2015) Norepinephrine is required to promote wakefulness and for hypocretin-induced arousal in zebrafish. eLIFE. 4:e07000.
Abstract
Pharmacological studies in mammals suggest that norepinephrine (NE) plays an important role in promoting arousal. However, the role of endogenous NE is unclear, with contradicting reports concerning the sleep phenotypes of mice lacking NE due to mutation of dopamine β-hydroxylase (dbh). To investigate NE function in an alternative vertebrate model, we generated dbh mutant zebrafish. In contrast to mice, these animals exhibit dramatically increased sleep. Surprisingly, despite an increase in sleep,dbh mutant zebrafish have a reduced arousal threshold. These phenotypes are also observed in zebrafish treated with small molecules that inhibit NE signaling, suggesting that they are caused by the lack of NE. Using genetic overexpression of hypocretin (Hcrt) and optogenetic activation of hcrt-expressing neurons, we also find that NE is important for Hcrt-induced arousal. These results establish a role for endogenous NE in promoting arousal and indicate that NE is a critical downstream effector of Hcrt neurons.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping