title: QRFP and Its Receptors Regulate Locomotor Activity and Sleep in Zebrafish.
abstract: The hypothalamus plays an important role in regulating sleep, but few hypothalamic sleep-promoting signaling pathways have been identified. Here we demonstrate a role for the neuropeptide QRFP (also known as P518 and 26RFa) and its receptors in regulating sleep in zebrafish, a diurnal vertebrate. We show that QRFP is expressed in ∼10 hypothalamic neurons in zebrafish larvae, which project to the hypothalamus, hindbrain, and spinal cord, including regions that express the two zebrafish QRFP receptor paralogs. We find that the overexpression of QRFP inhibits locomotor activity during the day, whereas mutation of qrfp or its receptors results in increased locomotor activity and decreased sleep during the day. Despite the restriction of these phenotypes to the day, the circadian clock does not regulate qrfp expression, and entrained circadian rhythms are not required for QRFP-induced rest. Instead, we find that QRFP overexpression decreases locomotor activity largely in a light-specific manner. Our results suggest that QRFP signaling plays an important role in promoting sleep and may underlie some aspects of hypothalamic sleep control.
  
  
  CONCLUSIONS
  The hypothalamus is thought to play a key role in regulating sleep in vertebrate animals, but few sleep-promoting signaling pathways that function in the hypothalamus have been identified. Here we use the zebrafish, a diurnal vertebrate, to functionally and anatomically characterize the neuropeptide QRFP. We show that QRFP is exclusively expressed in a small number of neurons in the larval zebrafish hypothalamus that project widely in the brain. We also show that QRFP overexpression reduces locomotor activity, whereas animals that lack QRFP signaling are more active and sleep less. These results suggest that QRFP signaling participates in the hypothalamic regulation of sleep.
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, and.
authors: Audrey
authors: http://orcid.org/0000-0003-2139-9535
authors: A
authors: Chen
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, and.
authors: Cindy N
authors: CN
authors: Chiu
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, and.
authors: Eric A
authors: EA
authors: Mosser
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, and.
authors: Sohini
authors: S
authors: Kahn
authors: Keck Science Department, Claremont McKenna, Pitzer and Scripps Colleges, Claremont, California 91711.
authors: Rory
authors: R
authors: Spence
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, and dprober@caltech.edu.
authors: David A
authors: DA
authors: Prober
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D017124:Conserved Sequence; D007031:Hypothalamus / Q000378:metabolism / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007814:Larva; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012249:Rhombencephalon / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology; D015027:Zebrafish / Q000502:physiology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C511787:QRFP peptide; D018000:Receptors, Peptide
keywords: 26RFa; Gpr103; P518; QRFP; sleep; zebrafish