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
  • Animals
  • Arousal/drug effects*
  • Autonomic Nervous System Diseases
  • Dopamine beta-Hydroxylase/deficiency
  • Dopamine beta-Hydroxylase/genetics
  • Dopamine beta-Hydroxylase/metabolism
  • Norepinephrine/deficiency
  • Norepinephrine/metabolism*
  • Orexins/metabolism*
  • Wakefulness/drug effects*
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed
26374985 Full text @ Elife
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
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes