Exploring phylogeny to find the function of sleep

Nature reviews. Neuroscience, Journal Year: 2018, Volume and Issue: 20(2), P. 109 - 116

Published: Dec. 20, 2018

Language: Английский

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Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit

Current Biology, Journal Year: 2019, Volume and Issue: 30(1), P. 1 - 16.e13

Published: Dec. 12, 2019

Language: Английский

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Sleep Counteracts Aging Phenotypes to Survive Starvation-Induced Developmental Arrest in C. elegans

Current Biology, Journal Year: 2018, Volume and Issue: 28(22), P. 3610 - 3624.e8

Published: Nov. 1, 2018

Sleep is ancient and fulfills higher brain functions as well basic vital processes. Little known about how sleep emerged in evolution what essential it was selected for. Here, we investigated Caenorhabditis elegans across developmental stages physiological conditions to find out when a simple animal becomes for survival. We found that worms occurs during most typically induced by the sleep-active RIS neuron. Food quality availability determine amount. Extended starvation, which induces arrest larvae, presents major trigger. Conserved nutrient-sensing regulators of longevity arrest, AMP-activated kinase FoxO, act parallel induce extended food deprivation. These metabolic factors can multiple tissues signal starvation RIS. Although does not appear be normal adult lifespan, crucial survival starvation-induced larvae. Rather than merely saving energy later use, counteracts progression aging phenotypes, perhaps allocating resources. Thus, protective anti-aging program pathways survive arrest. All organisms are threatened with possibility experienced famine their life, suggests molecular coupling development, aging, early nervous systems may conserved other species, including humans.

Language: Английский

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A salt-induced kinase is required for the metabolic regulation of sleep

PLoS Biology, Journal Year: 2020, Volume and Issue: 18(4), P. e3000220 - e3000220

Published: April 21, 2020

Many lines of evidence point to links between sleep regulation and energy homeostasis, but mechanisms underlying these connections are unknown. During Caenorhabditis elegans sleep, energetic stores allocated nonneural tasks with a resultant drop in the overall fat charge. Mutants lacking KIN-29, C. homolog mammalian Salt-Inducible Kinase (SIK) that signals pressure, have low ATP levels despite high-fat stores, indicating defective response cellular deficits. Liberating corrects adiposity defects kin-29 mutants. homeostasis roles map set sensory neurons act upstream as well central sleep-controlling neurons, suggesting hierarchical somatic/neural interactions regulating homeostasis. Genetic interaction histone deacetylase hda-4 coupled subcellular localization studies indicate KIN-29 acts nucleus regulate sleep. We propose KIN-29/SIK nuclei neuroendocrine cells transduce charge into mobilization which turn promotes

Language: Английский

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Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: 44(9), P. 1515 - 1531

Published: April 19, 2024

Accumulating evidence shows that most chronic neurological diseases have a link with sleep disturbances, and patients chronically poor undergo an accelerated cognitive decline. Indeed, single-night of deprivation may increase metabolic waste levels in cerebrospinal fluid. However, it remains unknown how disturbances isolation from underlying disease affect the glymphatic system. Clearance brain interstitial by system occurs primarily during sleep, driven multiple oscillators including arterial pulsatility, vasomotion. Herein, we induced fragmentation young wildtype mice assessed effects on activity functions. Chronic reduced function impaired functions healthy mice. A mechanistic analysis showed suppressed slow vasomotion, without altering cardiac-driven pulsations. Taken together, results this study document suppresses metabolite clearance impairs cognition, even absence disease.

Language: Английский

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A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 10, 2019

Abstract Animals must slow or halt locomotion to integrate sensory inputs change direction. In Caenorhabditis elegans , the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show functions additionally as a stop neuron. optogenetic stimulation caused acute persistent inhibition of pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides GABA. photoactivation allows animal maintain its body posture by sustaining muscle tone, yet inactivating motor oscillatory activity. During locomotion, axonal Ca2+ signals revealed functional compartmentalization: Activity in nerve ring process correlated with stop, while activity branch induced reversals. GABA was required induce, were sustain stop. attenuates neuronal inhibits movement, possibly enabling integration decision making, exemplifies dual use one cell across development compact nervous system.

Language: Английский

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Innate Immunity Promotes Sleep through Epidermal Antimicrobial Peptides

Current Biology, Journal Year: 2020, Volume and Issue: 31(3), P. 564 - 577.e12

Published: Nov. 30, 2020

Language: Английский

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Synaptic dysfunction connects autism spectrum disorder and sleep disturbances: A perspective from studies in model organisms

Sleep Medicine Reviews, Journal Year: 2022, Volume and Issue: 62, P. 101595 - 101595

Published: Jan. 25, 2022

Language: Английский

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Genetic sleep deprivation: using sleep mutants to study sleep functions

EMBO Reports, Journal Year: 2019, Volume and Issue: 20(3)

Published: Feb. 25, 2019

Review25 February 2019Open Access Genetic sleep deprivation: using mutants to study functions Henrik Bringmann Corresponding Author [email protected] orcid.org/0000-0002-7689-8617 Max Planck Institute for Biophysical Chemistry, Göttingen, Germany Search more papers by this author Information *,1 1Max *Corresponding author. Tel: +49 551 2011091; E-mail: EMBO Reports (2019)20:e46807https://doi.org/10.15252/embr.201846807 See the Glossary abbreviations used in article. PDFDownload PDF of article text and main figures. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Sleep is a fundamental conserved physiological state animals humans. It may serve multiple functions, ranging from energy conservation higher brain operation. Understanding underlying mechanisms requires sleeplessness its consequences. The traditional approach remove deprivation (SD) sensory stimulation. However, stimulation-induced SD can be stressful cause non-specific side effects. An emerging alternative method "genetic SD", which removes genetics or optogenetics. sleep-active neurons their regulators. Thus, genetic impairment circuits might lead specific comprehensive loss. Here, I discuss advantages limits key model animals: rodents, zebrafish, fruit flies roundworms, how alters our view functions. typically causes less severe phenotypes compared with SD, suggesting that have overestimated role sleep, calling re-investigation ALA name Caenorhabditis elegans interneuron/mechanosensory neuron AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid CNO clozapine-N-oxide dFB dorsal fan-shaped body EEG electroencephalogram EGF epidermal growth factor GABA γ-aminobutyric GPCR G protein-coupled receptor HPA hypothalamic–pituitary–adrenal axis MS medial septum PB parabrachial nuclei PI pars intercerebralis PZ parafacial zone REM rapid eye movement RIS ring interneuron s, C. ROS reactive oxygen species SIK3 salt-inducible kinase 3 VLPO ventrolateral preoptic nucleus Introduction We spend about one-third lives asleep. curtailment detrimental human health associated an increased risk infection, depression, cardiovascular disease, obesity, type 2 diabetes, cancer, illustrating importance time investment. high prevalence insomnia insufficient quality modern societies thus presents massive unmet problem 1234. appears affect virtually all aspects animal physiology, numerous processes been proposed depend on regular occurrence sleep. While broad consequences loss are obvious, there still no consensus as what direct are, carries out at molecular level. research first focused Seminal work recordings showed humans two types non-REM also called active quiet respectively. During shows asynchronous activity similar wake, concomitant paralysis striated muscles, few exceptions including musculature controlling breathing. both muscles show reduced highly synchronous 56. Using electrophysiological characteristics it has possible detect wide range mammals birds 78. Even reptiles possess different states resemble whereas amphibians appear only 9. This led conclusion diverged base amniotes into Behavioral quiescence long observed across species, invertebrates. defining correlates often not due anatomical differences. Nevertheless, identified four behavioral criteria 10. (i) A typical posture assumed compatible muscle activity. (ii) reduces responsiveness stimulation, indicating global neural dampening extends systems, contrasts wakefulness. (iii) rapidly reversible, meaning readily awoken, separating coma paralysis. (iv) under homeostatic regulation, implying exist ensure takes place, underscoring By applying these criteria, nervous system, cnidaria presenting most basal phylum detected 11. much widespread among than initially thought 12. Particularly important was identification three non-mammalian models, Drosophila, elegans, models facilitate mechanistic dissection 1314151617. Compelling evidence existence system but never sleeps lacking, amount plastic some get away little Environmental conditions impact need, spent differs substantially species. Under extreme conditions, temporary restriction even complete confers selective advantage. For example, migrating mating able suspend reduce need least several days 1819. Also, such large herbivores cave-dwelling fish, manage live sleeping little, h per day sufficient 2021. On other extreme, bats up 20 21. suggests adapted to, depends ecological constraints, perhaps regulate behavior preserve 22. Because asleep 10% time, lower limit required survival seems (Fig 1). Figure 1. fraction varies greatly does drop below 10%Sleep between 3–20 h/24 lot Model organisms fall within wild 3885103124. Download figure PowerPoint Functions underpinnings play roles coarsely sorted groups overlapping mutually exclusive. group function theories posits plays optimizing allocation energy. second core cellular processes. And third serves 1223 2). 2. Summary hypothesized sleepVarious ideas changes hypotheses depicted here. (A) In simple form, save when adaptive. would hibernation Energy saved later use could rather allocated anabolic reactions protein synthesis 25. (B) become adaptive compartmentalizing conflicting metabolic make efficient 36. controls hormones, food intake, metabolism (including lipid sugar metabolism) 34. cyclic biochemical reactions. Wakefulness, phosphorylation synaptic proteins dephosphorylation 37. Various homeostasis exist, accumulation extracellular adenosine 144. immune 323334. (C) plasticity learning memory. Synaptic during include downscaling weak synapses, process promoted Homer1a. Strong synapses preserved 4547145. support systems memory consolidation re-activating re-distributing areas 49. These re-arrangements novel insight creativity 50. Note overlapping. Most stems value understood viewing inactive state. At times wakefulness advantageous, organism enter strong argument energetic constraints determining variation intensity seen share energy-saving torpor, metabolically behaviorally phase found characterized temperature, instance hibernation. Both transitions torpor well exit involve they related 222425. differ defined reversible state, generally reversible. functional difference dissipate 2627. benefits cannot simply explained alone. According theory primarily diverted restorative biosynthetic 2528. becomes regenerative allowing facilitating housekeeping supported transcriptomic studies increase expression genes biosynthesis transport 293031. Anabolic could, growth, stress resistance, 32333435. control metabolism, part, regulating rhythmic timing intake. instance, increases concentration appetite-stimulating hormone ghrelin, appetite-inhibiting leptin, syndrome, diabetes itself present cycle, provides temporal compartmentalization difficult reconcile energetically favorable if carried subsequently example cycling reaction substantial proteins, globally wakefulness, decreased responsible cycle SIK3, gain-of-function mutation sleepy excessive duration 38. known regulator link 3940. Completing picture housekeeping, mice period potentially toxic molecules aggregates removed brain. removal neuronal shrinkage increasing flux interstitial fluid 41. experiments good night's Memory formation regions encode Transcriptome analysis brains formation, 424344. Plasticity involves alterations size composition synapses. new memories strengthen form weaken disappear. leads net synapse subsequent downscaling, mostly affects leaves intact 45. weakening receptors, Homer1a 46. working model, kept noradrenergic signaling enters recruitment adenosine, somnogenic (sleep-promoting) accumulate promotes drive 4748. Besides cell biological composition, occurs level involving recurrent reactivation redistribution integration existing circuits, updating knowledge. Disconnecting input restructuring mature allow associations creative insights problems hard solve help consolidate certain memories, that, mediated hippocampus, though 649. induced crucial induction. Research substrates started patients who had suffered consequence infection-induced injury. Lesions particular area, anterior hypothalamus, reduction demonstrating dedicated centers mammalian 51. motivated centers, cats, rats, mice. Central induction sleep-promoting express inhibitory neurotransmitters, GABA, neuropeptides. Sleep-active depolarize specifically onset inhibit wake-promoting promote inhibited stimulation arousal quick reversibility. They over-activated confer drive. motor turn regulated upstream driver determine 5253. reveals regarding based observations correlate causality established studying deprivation. wakefulness-promoting oppose each generate discrete 54. i.e., leading inhibition system. Stimulation-induced accounts causal testing summarized above. Acute essential Complete rodents caused weight loss, skin ulceration, sepsis, ultimately death experimental 55. To prevent lethality, applied partially shorten then restriction, imposed chronically Chronic understand effects chronic health. injury vigilance attribute partial stress. pleiotropic made impossible clearly deduce immediate Sleep, arousal, intimately linked hyperarousal mental mammals, activates sets off response, maintains suppresses perpetuating vicious 5758. Gentler protocols standard today aim arouse motivating instead stressing. achieved over pathways 3) 59. confounding after interference rebound wake pressure "lapses" "microsleep" bouts disturb deficits attention, memory, information processing 60. performance, whether defects directly mechanisms. 3. Classic impairs sleep-inducing systemAccording flip-flop switch antagonizing wake-inducing 52. dominates wake. Sensory suppressing despite (D) Genetically impairing permits disinhibition. contribute part normal waking ablation hyperarousal. arousing effect likely smaller hyperactivity manipulations without causing hyperactivity. approaches change fundamentally means complementary. should pursued establishing strategy render sleepless paradigm, lacks induction, requiring additional following attributable disinhibition 3). How impaired? ablate parts neurosurgical methods, way impair through targeting. call SD". deletion results lethality many either conditional approaches. Conditional generated optogenetic chemogenetic inducible knockouts create analog Alternatively, hypomorphic mutations analogs restriction. imminently lethal, choice phenotypes. As targeting directly, manipulating downstream employed removing achieved, activating preventing normally neurons. complement studies, devised activate gain". Specificity mutant phenotype indirectly. circadian rhythms abrogation result 6162. phenotype, will Similarly, strongly same 63. probably obtained mutating circuits. arousal. Assuming minor limiting prominent inducing moderate Consistent idea, (see below). specificity systems. degree long-term consequences, genetically tools organisms, high, complete. Homeostatic compensatory compensate depth remaining which, ameliorates Some relatively small amounts fulfill sleep's 2152. detectable residual advantageous bound. induces over-activation neurons, baseline 5464. systems: discoveries were variety mice, monkeys. pivotal structures turned conserved. Its amenability mouse intensively 236566. investigated mammals. rodent Forward screening Dreamless, dominant gene encodes ion channel excitability, GABAergic ventral medulla stem. Inhibition induce optogenetically depolarizing 67. Dreamless investigate yet published. Proving challenge because 6. involved high-amplitude theta waves hippocampal EEG. itself, silenced Silencing providing 68. optogenetics Mutants completely described, display very ideal 6269. gain 4). There principal triggering via successfully rodents. impaired. area PB, activated chemogenetically extend restrict 70. Alternatively extended supramammillary glutamatergic 71. lesioning approximately 50% stress, hyperarousal, 7273. controlled 74. Sleep-promoting indirectly, activation inhibitors lateral hypothalamus forebrain 7576. Other forebrain, stem, cortex contain 66. brainstem region shown sleep-active, 40%, 5) 777879. populations explain why subsets fascinating ablating reasonable next step combine ablations see stronger 4. modelsShown examples low specificity, levels do

Language: Английский

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Non-Visual Light Sensing Enhances Behavioral Memory and Drives Gene Expression in C. elegans

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Abstract Visible light influences a range of physiological processes, yet how animals respond to it independently the visual system remains largely unknown. Here, we uncover previously undescribed light-induced transcriptional pathway that modulates behavioral plasticity in C. elegans , roundworm without eyes. We demonstrate ambient visible or controlled-intensity visible-spectrum LED activates an effector gene cyp-14A5 non-neuronal tissues through bZIP transcription factors ZIP-2 and CEBP-2. Light induction is more prominent at shorter wavelengths but independent known blue receptors LITE-1 GUR-3 . This bZIP-dependent genetic enhances adaptability olfactory memory, suggesting body-brain communication axis. Furthermore, use light-responsive promoter drive ectopic expression, causing synthetic sleep rapid aging phenotypes These findings advance our understanding mechanisms outside offer new tool for light-inducible expression tissues.

Language: Английский

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