Editors' ChoiceNeuroscience

The Healing Power of Sleep

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Science Signaling  28 Oct 2014:
Vol. 7, Issue 349, pp. ec299
DOI: 10.1126/scisignal.aaa1491

Sleep has restorative powers. Studies from Hill et al. and Nelson et al. indicate that sleep is important for nematodes to recover from cellular stress. Hill et al. report that Caenorhabditis elegans exposed to noxious heat or cold, ethanol, or hyperosmotic stress ceased feeding and reduced their locomotor activity. After removal of the noxious stimulus, the animals entered a temporary sleep-like state, in which they became even more behaviorally quiescent and unresponsive to sensory stimulation, before returning to normal activities. Animals lacking the ALA neuron did not enter this sleep-like state following removal of the stressful stimulus. Epidermal growth factors (EGFs) have been implicated in inducing sleep in vertebrates, and overexpressing the EGF homolog lin-3 in C. elegans induces behavioral quiescence in a manner requiring the EGF receptor LET-23 and the EGF pathway mediator phospholipase C-γ (PLC-γ) in the ALA neuron. Compared with wild-type worms, worms with reduced LIN-3, LET-23, or PLC-γ were less quiescent during recovery from heat stress. Worms lacking the stress-responsive transcription factors HSF-1 or DAF-16 or the chaperone HSP-4 remained behaviorially quiescent longer than wild-type worms following heat stress, and worms lacking the ALA neuron or PLC-γ showed reduced survival following extreme heat stress. Nelson et al. found that depolarization of the ALA neuron was required for stress-induced behavioral quiescence, because silencing the ALA neuron by expressing a histamine-gated chloride channel in this cell repressed post-stress behavioral quiescence in the presence of histamine. Depolarizing ALA by expressing a light-activated cation channel in this neuron induced behavioral quiescence. The ALA neuron expressed flp-13, which encodes a neuropeptide related to FMRFamide, and heat shock increased the expression of flp-13. FLP-13 was required in the ALA neuron for behavorial quiescence following heat stress, and flp-13 mutants showed reduced quiescence in response to lin-3 overexpression. Finally, animals overexpressing flp-13 were more behaviorally quiescent than wild-type animals following mild heat stress. A membrane-tethered form of LIN-3 that is present in the pharynx can be proteolytically cleaved to release the active EGF domain. The authors hypothesize that heat stress induces the cleavage and release of LIN-3, which activates LET-23 on the ALA neuron, leading to depolarization and release of FLP-13, which induces quiescence. Not only do these findings confirm that sleep serves a protective function that allows for the recovery from cellular stress, they suggest a mechanism by which cellular stress reversibly induces sleep.

A. J. Hill, R. Mansfield, J. M. N. G. Lopez, D. M. Raizen, C. Van Buskirk, Cellular stress induces a protective sleep-like state in Celegans. Curr. Biol. 24, 2399–2405 (2014). [PubMed]

M. D. Nelson, K. H. Lee, M. A. Churgin, A. J. Hill, C. Van Buskirk, C. Fang-Yen, D. M. Raizen, FMRFamide-like FLP-13 neuropeptides promote quiescence following heat stress in Caenorhabditis elegans. Curr. Biol. 24, 2406–2410 (2014). [PubMed]

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