ZFIN ID: ZDB-PUB-091215-50
Sleep-wake regulation and hypocretin-melatonin interaction in zebrafish
Appelbaum, L., Wang, G.X., Maro, G.S., Mori, R., Tovin, A., Marin, W., Yokogawa, T., Kawakami, K., Smith, S.J., Gothilf, Y., Mignot, E., and Mourrain, P.
Date: 2009
Source: Proc. Natl. Acad. Sci. USA 106(51): 21942-21947 (Journal)
Registered Authors: Kawakami, Koichi, Mourrain, Philippe
Keywords: pineal gland, sleep consolidation
MeSH Terms:
  • Animals
  • Intracellular Signaling Peptides and Proteins/physiology*
  • Melatonin/biosynthesis
  • Melatonin/physiology*
  • Neuropeptides/physiology*
  • Orexin Receptors
  • Orexins
  • Pineal Gland/metabolism
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism
  • Receptors, G-Protein-Coupled/physiology
  • Receptors, Neuropeptide/genetics
  • Receptors, Neuropeptide/metabolism
  • Receptors, Neuropeptide/physiology
  • Sleep*
  • Wakefulness*
  • Zebrafish/physiology*
PubMed: 19966231 Full text @ Proc. Natl. Acad. Sci. USA
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ABSTRACT
In mammals, hypocretin/orexin (HCRT) neuropeptides are important sleep-wake regulators and HCRT deficiency causes narcolepsy. In addition to fragmented wakefulness, narcoleptic mammals also display sleep fragmentation, a less understood phenotype recapitulated in the zebrafish HCRT receptor mutant (hcrtr-/-). We therefore used zebrafish to study the potential mediators of HCRT-mediated sleep consolidation. Similar to mammals, zebrafish HCRT neurons express vesicular glutamate transporters indicating conservation of the excitatory phenotype. Visualization of the entire HCRT circuit in zebrafish stably expressing hcrt:EGFP revealed parallels with established mammalian HCRT neuroanatomy, including projections to the pineal gland, where hcrtr mRNA is expressed. As pineal-produced melatonin is a major sleep-inducing hormone in zebrafish, we further studied how the HCRT and melatonin systems interact functionally. mRNA level of arylalkylamine-N-acetyltransferase (AANAT2), a key enzyme of melatonin synthesis, is reduced in hcrtr-/- pineal gland during the night. Moreover, HCRT perfusion of cultured zebrafish pineal glands induces melatonin release. Together these data indicate that HCRT can modulate melatonin production at night. Furthermore, hcrtr-/- fish are hypersensitive to melatonin, but not other hypnotic compounds. Subthreshold doses of melatonin increased the amount of sleep and consolidated sleep in hcrtr-/- fish, but not in the wild-type siblings. These results demonstrate the existence of a functional HCRT neurons-pineal gland circuit able to modulate melatonin production and sleep consolidation.
ADDITIONAL INFORMATIONNo data available