Lethargus is a Caenorhabditis elegans sleep-like state

Raizen, David M.; Zimmerman, John E.; Maycock, Matthew H.; Ta, Uyen D.; You, Young-Jai; Sundaram, Meera V.; Pack, Allan I.

doi:10.1038/nature06535

Cited by 473 publications

(648 citation statements)

References 29 publications

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“…This plastic behavior is correlated to PKG enzyme activity and pharmacological manipulations of PKG activity change this behavioral plasticity (Lucas and Sokolowski, 2009). In C. elegans, PKG plays a role in olfactory adaptation as well as other plastic phenotypes (Fujiwara et al, 2002;L'Etoile et al, 2002;Hirose et al, 2003;Raizen et al, 2008). In the honey bee, for plays a role in the long-term plasticity changes involved in the switch from nursing to foraging (Ben-Shahar et al, 2002.…”

Section: Discussionmentioning

confidence: 99%

“…Phase differences are also related to thermotolerance in locusts, including, for example, expression of heat shock proteins (Wang et al, 2007) and response to pathogens (Elliot et al, 2003(Elliot et al, , 2005. PKG is also involved in phototaxis behavior in bees (Ben-Shahar et al, 2003) and in circadian clock-related behaviors such as quiescence or sleep in both C. elegans and D. melanogaster (e.g., Raizen et al, 2008). In locusts, gregarious animals are characterized by diurnal flight behavior, while solitary locusts fly at night.…”

Section: Discussionmentioning

confidence: 99%

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The locust foraging gene

Lucas

Kornfein

Chakaborty-Chatterjee

et al. 2010

Arch Insect Biochem Physiol

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Our knowledge of how genes act on the nervous system in response to the environment to generate behavioral plasticity is limited. A number of recent advancements in this area concern food-related behaviors and a specific gene family called foraging (for), which encodes a cGMPdependent protein kinase (PKG). The desert locust (Schistocerca gregaria) is notorious for its destructive feeding and long-term migratory behavior. Locust phase polyphenism is an extreme example of environmentally induced behavioral plasticity. In response to changes in population density, locusts dramatically alter their behavior, from solitary and relatively sedentary behavior to active aggregation and swarming. Very little is known about the molecular and genetic basis of this striking behavioral phenomenon. Here we initiated studies into the locust for gene by identifying, cloning, and studying expression of the gene in the locust brain. We determined the phylogenetic relationships between the locust PKG and other known PKG proteins in insects. FOR expression was found to be confined to neurons of the anterior midline of the brain, the pars intercerebralis. Our results suggest that differences in PKG enzyme activity are correlated to well-established phase-related behavioral differences. These results lay the groundwork for functional studies of the locust for gene and its possible relations to locust phase polyphenism.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The locust foraging gene

Lucas

Kornfein

Chakaborty-Chatterjee

et al. 2010

Arch Insect Biochem Physiol

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“…( 2017), Tropini, Earle, Huang and Sonnenburg ( 2017); excretory system: King and Goldstein (1985), Buechner (2002), Gautam, Verma and Tapadia ( 2017); sleep and circadian system: Raizen et al. ( 2008); Trojanowski and Raizen (2016); Miyazaki, Liu and Hayashi ( 2017); others: Micchelli and Perrimon (2006), Ohlstein and Spradling (2006), Chaturvedi, Reichert, Gunage and VijayRaghavan ( 2017), Gunage, Dhanyasi, Reichert and VijayRaghavan (2017)…”

Section: Research Organisms For Agingmentioning

confidence: 99%

The African turquoise killifish: A research organism to study vertebrate aging and diapause

Brunet²

2018

Aging Cell

132

118

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SummaryThe African turquoise killifish has recently gained significant traction as a new research organism in the aging field. Our understanding of aging has strongly benefited from canonical research organisms—yeast, C. elegans, Drosophila, zebrafish, and mice. Many characteristics that are essential to understand aging—for example, the adaptive immune system or the hypothalamo‐pituitary axis—are only present in vertebrates (zebrafish and mice). However, zebrafish and mice live more than 3 years and their relatively long lifespans are not compatible with high‐throughput studies. Therefore, the turquoise killifish, a vertebrate with a naturally compressed lifespan of only 4–6 months, fills an essential gap to understand aging. With a recently developed genomic and genetic toolkit, the turquoise killifish not only provides practical advantages for lifespan and longitudinal experiments, but also allows more systematic characterizations of the interplay between genetics and environment during vertebrate aging. Interestingly, the turquoise killifish can also enter a long‐term dormant state during development called diapause. Killifish embryos in diapause already have some organs and tissues, and they can last in this state for years, exhibiting exceptional resistance to stress and to damages due to the passage of time. Understanding the diapause state could give new insights into strategies to prevent the damage caused by aging and to better preserve organs, tissues, and cells. Thus, the African turquoise killifish brings two interesting aspects to the aging field—a compressed lifespan and a long‐term resistant diapause state, both of which should spark new discoveries in the field.

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“…C. elegans ($300 neurons) has a quiescent behavioral state during a period called lethargus. [260][261][262] It occurs before each of the four molts and exhibits some aspects of sleep, including higher arousal thresholds and a homeostatic response to mechanical stimulation during lethargus (specifically, an augmented quiescence after stimulation). 260 The periods of lethargus involve alterations of the worm's nervous system, suggesting that lethargus evolved to accommodate specific requirements of such alterations.…”

Section: Protein Fragments and The Size Of A Nervous Systemmentioning

confidence: 99%

“…[260][261][262][263][264] The FG hypothesis predicts higher levels of specific protease-generated protein fragments in some or most C. elegans neurons (and possibly in other cell types as well) shortly before lethargus. If the FG hypothesis proves relevant to the causation and function of sleep in mammals, the resulting understanding could be ''turned around'' by asking whether the lethargus in C. elegans involves the generation and degradation of specific fragments and the remodeling of protein complexes after fragments' removal, and whether these processes are the molecular cause of lethargus.…”

Section: Protein Fragments and The Size Of A Nervous Systemmentioning

confidence: 99%

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Varshavsky

2012

Protein Science

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Despite extensive understanding of sleep regulation, the molecular-level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca 21 fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca 21 -activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca 21 transients) while fragment-destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness-increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol-induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca 21 alone or Ca 21 and its ionophore (Erickson et al., Science 1978;199:1219-1221 Harris, Pharmacol Biochem Behav 1979;10:527-534; Erickson et al., Pharmacol Biochem Behav 1980;12:651-656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.

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Lethargus is a Caenorhabditis elegans sleep-like state

Cited by 473 publications

References 29 publications

The locust foraging gene

The locust foraging gene

The African turquoise killifish: A research organism to study vertebrate aging and diapause

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

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