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Neuron. 2016 Feb 17;89(4):842-56. doi: 10.1016/j.neuron.2016.01.007.

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

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
2
Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, UK; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
3
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
4
Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
5
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Division of Sleep Medicine, Harvard University, Cambridge, MA 02138, USA. Electronic address: schier@fas.harvard.edu.
6
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: dprober@caltech.edu.

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.

PMID:
26889812
PMCID:
PMC4851465
DOI:
10.1016/j.neuron.2016.01.007
[Indexed for MEDLINE]
Free PMC Article

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