PUBLICATION

A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States

Authors
Chiu, C.N., Rihel, J., Lee, D.A., Singh, C., Mosser, E.A., Chen, S., Sapin, V., Pham, U., Engle, J., Niles, B.J., Montz, C.J., Chakravarthy, S., Zimmerman, S., Salehi-Ashtiani, K., Vidal, M., Schier, A.F., Prober, D.A.
ID
ZDB-PUB-160219-7
Date
2016
Source
Neuron   89: 842-856 (Journal)
Registered Authors
Prober, David, Rihel, Jason, Schier, Alexander, Zimmerman, Steve
Keywords
none
MeSH Terms
  • Age Factors
  • Aniline Compounds/pharmacology
  • Animals
  • Brain Stem/cytology
  • Brain Stem/growth & development
  • Brain Stem/metabolism
  • Gene Expression Regulation/drug effects
  • Gene Expression Regulation/genetics*
  • Humans
  • Hypothalamo-Hypophyseal System/metabolism
  • Larva
  • Mice, Transgenic
  • Motor Activity/genetics
  • Neurons/drug effects
  • Neurons/metabolism
  • Neuropeptides/genetics*
  • Neuropeptides/metabolism*
  • Pituitary-Adrenal System/metabolism
  • Pyrimidines/pharmacology
  • Receptors, Complement 3b/metabolism
  • Receptors, Neurotransmitter/metabolism
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Sleep/genetics*
  • Wakefulness/genetics*
  • Zebrafish
  • Zebrafish Proteins/genetics
PubMed
26889812 Full text @ Neuron
Abstract
Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu-induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway. VIDEO ABSTRACT.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes