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
  • Dopamine beta-Hydroxylase/deficiency
  • Dopamine beta-Hydroxylase/genetics
  • Dopamine beta-Hydroxylase/metabolism
  • Norepinephrine/deficiency
  • Norepinephrine/metabolism*
  • Autonomic Nervous System Diseases
  • Wakefulness/drug effects*
  • Arousal/drug effects*
  • Orexins/metabolism*
  • Zebrafish/genetics
  • Zebrafish/physiology*
(all 12)
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
Figure Gallery (2 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ct806
    Insertion
    ct819TgTransgenic Insertion
      ct821TgTransgenic Insertion
        ct831TgTransgenic Insertion
          hu2098
            Point Mutation
            zf11TgTransgenic Insertion
              zf12TgTransgenic Insertion
                1 - 7 of 7
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                No data available
                Fish
                Antibodies
                Name Type Antigen Genes Isotypes Host Organism
                Ab1-hcrtpolyclonal
                  Rabbit
                  1 - 1 of 1
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                  Orthology
                  Gene Orthology
                  dbh
                  1 - 1 of 1
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                  Engineered Foreign Genes
                  Marker Marker Type Name
                  EGFPEFGEGFP
                  EYFPEFGEYFP
                  RFPEFGRFP
                  1 - 3 of 3
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                  Mapping