Neuronal Machinery of Sleep Homeostasis in Drosophila

Donlea, Jeffrey M.; Pimentel, Diogo; Miesenböck, Gero

doi:10.1016/j.neuron.2014.03.008

Cited by 95 publications

(166 citation statements)

References 11 publications

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“…Induction of dFB activity induces sleep states that can even enhance memory consolidation (Donlea et al 2009). Sleep deprivation further enhances the activity of dFB neurons (Donlea et al 2014). The effects of sleep loss depend on the RhoGTPase-activating protein, CROSS-VEINLESS-C (CV-C) whose function also strongly affects baseline sleep (Donlea et al 2014).…”

Section: Acetylcholinementioning

confidence: 99%

“…Sleep deprivation further enhances the activity of dFB neurons (Donlea et al 2014). The effects of sleep loss depend on the RhoGTPase-activating protein, CROSS-VEINLESS-C (CV-C) whose function also strongly affects baseline sleep (Donlea et al 2014). dFB neurons are inhibited by key arousal promoting dopaminergic neurons via activation of the potassium "leak" current carried by Sandman, a two-pore potassium channel, and the suppression of voltage-gated A-type potassium current likely encoded in part by Sh (Pimentel et al 2016).…”

Section: Acetylcholinementioning

confidence: 99%

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Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Allada¹,

Cirelli

Sehgal

2017

Cold Spring Harb Perspect Biol

133

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Section: Acetylcholinementioning

confidence: 99%

Section: Acetylcholinementioning

confidence: 99%

Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Allada¹,

Cirelli

Sehgal

2017

Cold Spring Harb Perspect Biol

133

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“…Although this is the first study to uncover a role for a Vav protein in regulation of a sleep-like or quiescence behavior, a Rho-family GTPase guanine nucleotide-activating protein encoded by the crossveinless-c gene was recently implicated in sleep homeostasis in Drosophila (Donlea et al 2014), suggesting a conserved role for Rho-family GTPases in sleep behavior. Furthermore, Vav2 and Vav3 transcripts are expressed in regions of the human and mouse brain associated with sleep (Lein et al 2007;Hawrylycz et al 2012), such as the thalamus (Fuentealba and Steriade 2005).…”

Section: Discussionmentioning

confidence: 97%

A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence inCaenorhabditis elegans

et al. 2016

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Sleep is evolutionarily conserved and required for organism homeostasis and survival. Despite this importance, the molecular and cellular mechanisms underlying sleep are not well understood. Caenorhabditis elegans exhibits sleep-like behavioral quiescence and thus provides a valuable, simple model system for the study of cellular and molecular regulators of this process. In C. elegans, epidermal growth factor receptor (EGFR) signaling is required in the neurosecretory neuron ALA to promote sleep-like behavioral quiescence after cellular stress. We describe a novel role for VAV-1, a conserved guanine nucleotide exchange factor (GEF) for Rho-family GTPases, in regulation of sleep-like behavioral quiescence. VAV-1, in a GEF-dependent manner, acts in ALA to suppress locomotion and feeding during sleep-like behavioral quiescence in response to cellular stress. Additionally, VAV-1 activity is required for EGF-induced sleep-like quiescence and normal levels of EGFR and secretory dense core vesicles in ALA. Importantly, the role of VAV-1 in promoting cellular stress-induced behavioral quiescence is vital for organism health because VAV-1 is required for normal survival after cellular stress.KEYWORDS behavioral quiescence; Caenorhabditis elegans; sleep; Vav D ESPITE being a subject of formal study for over 150 years, sleep is not clearly understood. Moreover, various explanations for the functional role of sleep have been proposed, such as allowing "recharging" of cells following high metabolic activity (Benington and Heller 1995;Tu and McKnight 2006;Scharf et al. 2008) and remodeling of synapses built during wakefulness (Tononi and Cirelli 2006). Yet sleep problems have a significant impact on human health and are a leading reason for seeking medical attention (Mahowald and Schenck 2005). Therefore, there is a great need for understanding the cellular and molecular mechanisms that regulate sleep-wake cycles.Simple model organisms such as Caenorhabditis elegans have the potential to provide valuable information regarding sleep regulation. C. elegans is known for its easily manipulated genetics, small nervous system with mapped neuronal connectivity, stereotypical behaviors, and the ability to be studied efficiently in large numbers. Numerous studies have shown that C. elegans lethargus, a restful period that occurs before each molt of the cuticle during larval development, is neuronally regulated and likely orthologous to sleep in mammals (Van Buskirk and Sternberg 2007;Raizen et al. 2008;Van Buskirk and Sternberg 2010;Choi et al. 2013;Iwanir et al. 2013;Turek et al. 2013;Cho and Sternberg 2014;Singh et al. 2014). Lethargus quiescence in C. elegans shares several characteristics with mammalian sleep: inactivity (decreased locomotion and cessation of pharyngeal pumping, or feeding), a specific posture, reduced response to aversive stimuli, and rapid reversibility (Cassada and Russell 1975;Raizen et al. 2008;Schwarz et al. 2012;Iwanir et al. 2013;Cho and Sternberg 2014). In addition, lethargus quiescence is under ...

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“…We have recently shown that specific circadian neurons in the fly brain promote sleep by inhibiting other wake-promoting circadian neurons, and that this interplay between circadian neurons is a major feature of the circadian regulation of sleep (Guo et al 2016). Although these studies do not impact on homeostatic regulation, the fly is also beginning to illuminate the principles that underlie this mysterious process (e.g., Donlea et al 2014). As we originally learned from developmental biological studies and then from circadian biology, the fly may once again provide insights that will illuminate the mammalian landscape, in this case for the function and regulation of sleep.…”

mentioning

confidence: 99%

A 50-Year Personal Journey: Location, Gene Expression, and Circadian Rhythms

Rosbash

2017

Cold Spring Harb Perspect Biol

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Neuronal Machinery of Sleep Homeostasis in Drosophila

Cited by 95 publications

References 11 publications

Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

A Conserved GEF for Rho-Family GTPases Acts in an EGF Signaling Pathway to Promote Sleep-like Quiescence inCaenorhabditis elegans

A 50-Year Personal Journey: Location, Gene Expression, and Circadian Rhythms

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