A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 4519615
Author(s) Chiu, Cindy N.; Rihel, Jason; Lee, Daniel A.; Singh, Chanpreet; Mosser, Eric A.; Chen, Shijia; Sapin, Viveca; Pham, Uyen; Engle, Jae; Niles, Brett J.; Montz, Christin J.; Chakravarthy, Sridhara; Zimmerman, Steven; Salehi-Ashtiani, Kourosh; Vidal, Marc; Schier, Alexander F.; Prober, David A.
Author(s) at UniBasel Schier, Alexander
Year 2016
Title A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States
Journal Neuron
Volume 89
Number 4
Pages / Article-Number 842-856
Mesh terms Age Factors; Aniline Compounds, pharmacology; Animals; Brain Stem, cytology, growth & development, metabolism; Gene Expression Regulation, drug effects, genetics; Humans; Hypothalamo-Hypophyseal System, metabolism; Larva; Mice, Transgenic; Motor Activity, genetics; Neurons, drug effects, metabolism; Neuropeptides, genetics, metabolism; Pituitary-Adrenal System, metabolism; Pyrimidines, pharmacology; Receptors, Complement 3b, metabolism; Receptors, Neurotransmitter, metabolism; Signal Transduction, drug effects, genetics; Sleep, genetics; Wakefulness, genetics; Zebrafish; Zebrafish Proteins, genetics
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.
ISSN/ISBN 1097-4199
URL https://www.sciencedirect.com/science/article/pii/S0896627316000088
edoc-URL https://edoc.unibas.ch/74122/
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.neuron.2016.01.007
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/26889812

MCSS v5.8 PRO. 0.442 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |