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Curr Biol. 2016 Sep 26;26(18):2446-2455. doi: 10.1016/j.cub.2016.07.048. Epub 2016 Aug 18.

C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853-2703, USA.
2
Department of Molecular Biology and Genetics, Biotechnology 351, Cornell University, Ithaca, NY 14853-2703, USA.
3
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, Cornell University, Ithaca, NY 14853-2703, USA. Electronic address: pws@caltech.edu.

Abstract

The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep-pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus-and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides.

KEYWORDS:

RFamides; genetic redundancy; neuropeptide modulation; single-neuron RNA-seq; sleep regulation

PMID:
27546573
PMCID:
PMC5694219
DOI:
10.1016/j.cub.2016.07.048
[Indexed for MEDLINE]
Free PMC Article

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