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| Open AccessKnockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice
Uygun et al. show that deletion of GABAA receptors from the thalamic reticular nucleus using CRISPR gene editing in mice boosts the delta waves, indicating a role for GABAA receptors on thalamic reticular nucleus neurons in NREM sleep delta oscillations.
- David S. Uygun
- , Chun Yang
- & Radhika Basheer
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Article
| Open AccessA natural timeless polymorphism allowing circadian clock synchronization in “white nights”
The genus Drosophila originate in subSaharan Africa and spread North up to the polar circle where they experience long days in the summer or even constant light. Here, the authors show that a form of the TIMELESS protein enables flies to synchronise their behavioural activity to long summer days
- Angelique Lamaze
- , Chenghao Chen
- & Ralf Stanewsky
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Article
| Open AccessUBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony
Although ubiquitin ligases are known to control clock protein degradation, their other roles in clock neurons are unclear. Here the authors report that UBR4 promotes export of neuropeptides from the Golgi for axonal trafficking, which is important for circadian clock synchrony in mice and flies.
- Sara Hegazi
- , Arthur H. Cheng
- & Hai-Ying Mary Cheng
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Article
| Open AccessQuantifying arousal and awareness in altered states of consciousness using interpretable deep learning
The authors propose an explainable consciousness indicator using deep learning to quantify arousal and awareness under sleep, anesthesia, and in patients with disorders of consciousness.
- Minji Lee
- , Leandro R. D. Sanz
- & Seong-Whan Lee
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Article
| Open AccessCircadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin
A key property of circadian rhythms is that they can be reset in response to environmental time cues; this response is described by a Phase Response Curve (PRC). Here the authors describe PRCs for resetting circadian rhythms in lipids and hepatic proteins in response to combined light and food exposure.
- Brianne A. Kent
- , Shadab A. Rahman
- & Steven W. Lockley
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Article
| Open AccessBreathing coordinates cortico-hippocampal dynamics in mice during offline states
Using large-scale recordings from cortical and subcortical brain regions in behaving mice, the authors reveal the presence of a respiratory corollary discharge in mice, that modulates neural activity across these circuits and couples hippocampal sharp-wave ripples and cortical DOWN/UP state transitions.
- Nikolaos Karalis
- & Anton Sirota
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Article
| Open AccessCircadian neurons in the paraventricular nucleus entrain and sustain daily rhythms in glucocorticoids
It is unclear how circadian signals from the suprachiasmatic nucleus (SCN) are decoded to generate daily rhythms in hormone release. Here, the authors show that daily corticosterone release depends on coordinated clock gene and neuronal activity rhythms in both SCN and paraventricular nucleus neurons.
- Jeff R. Jones
- , Sneha Chaturvedi
- & Erik D. Herzog
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Article
| Open AccessNeurofibromin 1 in mushroom body neurons mediates circadian wake drive through activating cAMP–PKA signaling
The molecular mechanism by which clock neurons transmit timing information to non-clock neurons is poorly understood. Here, the authors show that circadian clocks drive rhythmic expression of hundreds of genes in mushroom body neurons and drive calcium rhythms via NF1-cAMP/PKAC1 signalling in Drosophila.
- Pedro Machado Almeida
- , Blanca Lago Solis
- & Emi Nagoshi
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Article
| Open AccessIdentification of the suprachiasmatic nucleus venous portal system in the mammalian brain
The first known portal system in the mammalian brain was identified in 1933. Here the authors describe a new portal system between the capillary beds of the Suprachiasmatic Nucleus master clock and a circumventricular organ, enabling humoral signals to reach targets without dilution in the systemic circulation.
- Yifan Yao
- , Alana B’nai Taub
- & Rae Silver
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Article
| Open AccessThe retinal ipRGC-preoptic circuit mediates the acute effect of light on sleep
The preoptic area (POA) is critical for sleep regulation but its role in acute, non-circadian, light effects on sleep are unclear. The authors show that intrinsically photosensitive retinal ganglion cells provide substantial input into the POA and through these modulate the amount of non-rapid eye movement (NREM) sleep.
- Ze Zhang
- , Corinne Beier
- & Samer Hattar
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Article
| Open AccessCognitive functions and underlying parameters of human brain physiology are associated with chronotype
How being a “morning person” or “evening person” affects human cognition and brain physiology is not well understood. Here the authors show evidence of an association of chronotype with cognitive functions and related physiological parameters.
- Mohammad Ali Salehinejad
- , Miles Wischnewski
- & Michael A. Nitsche
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Article
| Open AccessMicroglia modulate stable wakefulness via the thalamic reticular nucleus in mice
Here, the authors show that microglia depletion results in unstable wakefulness and altered levels of ceramide, influencing microglia in the mouse thalamic reticular nucleus (TRN). Stable wakefulness can be restored by activation of the TRN or inhibition of ceramide production in the mouse brain.
- Hanxiao Liu
- , Xinxing Wang
- & Qiaojie Xiong
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Article
| Open AccessReward biases spontaneous neural reactivation during sleep
Sleep is known to promote memory consolidation, but the extent to which this is dependent on the memory’s relevance remains unclear. Here, the authors use a brain decoding approach to show that neural representations of rewarded experiences undergo a privileged reactivation during sleep, favouring their consolidation.
- Virginie Sterpenich
- , Mojca K. M. van Schie
- & Sophie Schwartz
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Article
| Open AccessPredicting lapses of attention with sleep-like slow waves
Attentional lapses occur in many forms such as mind-wandering or mindblanking. Here the authors show different types of attentional lapse are accompanied by slow waves, neural activity that is characteristic of transitions into sleep.
- Thomas Andrillon
- , Angus Burns
- & Naotsugu Tsuchiya
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Article
| Open AccessEndogenous memory reactivation during sleep in humans is clocked by slow oscillation-spindle complexes
Sleep after learning helps to strengthen new memories. Here, the authors link this memory benefit to the reactivation of learning experiences when two endogenous sleep rhythms—slow oscillations and sleep spindles—coincide.
- Thomas Schreiner
- , Marit Petzka
- & Bernhard P. Staresina
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Review Article
| Open AccessImportance of circadian timing for aging and longevity
Circadian clocks link physiologic processes to environmental conditions and a mismatch between internal and external rhythms has negative effects on organismal health. In this review, the authors discuss the interactions between circadian clocks and dietary interventions targeted to promote healthy aging.
- Victoria A. Acosta-Rodríguez
- , Filipa Rijo-Ferreira
- & Joseph S. Takahashi
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Article
| Open AccessNet decrease in spine-surface GluA1-containing AMPA receptors after post-learning sleep in the adult mouse cortex
The synaptic mechanisms of how sleep benefits cognitive functions are not well characterised. Here, the authors show that sleep leads to an overall net decrease in spine-surface GluA1-containing AMPA receptors and that this is correlated with changes in performance after sleep.
- Daisuke Miyamoto
- , William Marshall
- & Chiara Cirelli
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Article
| Open AccessDistinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia
Cardiac function fluctuates greatly across the day and night, but this is not simply a consequence of our changing behaviour. The authors highlight the role of the body’s circadian clock in regulating the heart electrical activity, including a time-of-day dependent susceptibility to cardiac arrhythmias.
- Edward A. Hayter
- , Sophie M. T. Wehrens
- & David A. Bechtold
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Article
| Open AccessAdenosine integrates light and sleep signalling for the regulation of circadian timing in mice
Sleep pressure and circadian rhythms influence one another. However, the regulatory mechanisms are unclear. Here, the authors show that adenosine A1/A2A receptor antagonists, such as caffeine, shift circadian rhythms and enhance the effects of light, providing a molecular link between sleep pressure and circadian rhythm.
- Aarti Jagannath
- , Norbert Varga
- & Sridhar R. Vasudevan
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Article
| Open AccessGraded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve
Despite its wide and growing use, the mechanisms by which in vivo vagus nerve stimulation (VNS) exerts its therapeutic benefits are still largely unknown. Here, the authors show in mice that pupil dilation is a reliable and noninvasive biosensor for titratable VNS-evoked cortical neuromodulation by acetylcholine.
- Zakir Mridha
- , Jan Willem de Gee
- & Matthew James McGinley
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Article
| Open AccessCausal role for sleep-dependent reactivation of learning-activated sensory ensembles for fear memory consolidation
Learning-activated engram neurons play a critical role in memory recall but the role of these neurons in offline memory consolidation is unclear. The authors show that sleep-associated reactivation of learning-activated sensory neurons is necessary for memory consolidation.
- Brittany C. Clawson
- , Emily J. Pickup
- & Sara J. Aton
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Article
| Open AccessTravelling spindles create necessary conditions for spike-timing-dependent plasticity in humans
Sleep spindles during non-rapid eye movement are important for memory consolidation and require specific neuronal firing conditions in non-human mammals. Here, the authors show these conditions are present in humans, potentially facilitating spike-timing-dependent plasticity.
- Charles W. Dickey
- , Anna Sargsyan
- & Eric Halgren
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Article
| Open AccessGenetic determinants of daytime napping and effects on cardiometabolic health
The genetic basis of daytime napping and the directional effect of daytime napping on cardiometabolic health are unknown. Here, the authors perform a genome-wide association study on self-reported daytime napping in the UK Biobank and Mendelian randomization to explore causal associations.
- Hassan S. Dashti
- , Iyas Daghlas
- & Richa Saxena
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Article
| Open AccessStructures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation
Agonists of the orexin receptor 2 (OX2R) show promise in the treatment of narcolepsy. Cryo-EM structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist suggest a molecular mechanism that rationalizes both receptor activation and inhibition.
- Chuan Hong
- , Noel J. Byrne
- & Kaspar Hollenstein
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Article
| Open AccessA circadian clock regulates efflux by the blood-brain barrier in mice and human cells
The blood-brain barrier is critical for neural function. Here, the authors show that efflux of xenobiotics through the BBB follows a circadian rhythm in mice and human cells.
- Shirley L. Zhang
- , Nicholas F. Lahens
- & Amita Sehgal
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Article
| Open AccessA role for spindles in the onset of rapid eye movement sleep
During NREM sleep, spindles emerge from thalamocortical interactions. Here the authors carry out multisite thalamic and cortical recordings in freely behaving mice, to investigate the role of other non-classical thalamic sites in sleep spindle generation.
- Mojtaba Bandarabadi
- , Carolina Gutierrez Herrera
- & Antoine R. Adamantidis
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Article
| Open AccessSuprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations
Cell groups in the hypothalamic suprachiasmatic clock contribute to the genesis of circadian rhythms. The authors identified two populations of vasoactive intestinal polypeptide-expressing neurons in the suprachiasmatic nucleus which regulate locomotor circadian rhythm in mice.
- William D. Todd
- , Anne Venner
- & Patrick M. Fuller
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Article
| Open AccessCircadian control of brain glymphatic and lymphatic fluid flow
Glymphatic function is increased during the rest phase while more cerebrospinal fluid (CSF) drains directly to the lymphatic system during the active phase. The water channel aquaporin-4 supports these endogenous, circadian rhythms in CSF distribution.
- Lauren M. Hablitz
- , Virginia Plá
- & Maiken Nedergaard
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Article
| Open AccessOrexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep
Orexin signaling is provided by diffusely distributed fibers and involved in different brain circuits that orchestrate sleep and wakefulness states. Here, the authors show that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus and exhibit rapid eye movement (REM) sleep-related actions.
- Hui Feng
- , Si-Yi Wen
- & Jun Zhang
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Article
| Open AccessThe circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders
Antenatal glucocorticoid therapy is indicated for mothers at risk of preterm delivery. Here, the authors show that the circadian phase of antenatal glucocorticoid treatment affects the risk of behavioral disorders later in life in mice and in a retrospective observational study in human infants.
- Mariana Astiz
- , Isabel Heyde
- & Henrik Oster
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Article
| Open AccessThe VIP-VPAC2 neuropeptidergic axis is a cellular pacemaking hub of the suprachiasmatic nucleus circadian circuit
Circadian activity modulation in the suprachiasmatic nucleus (SCN) is a network-level emergent property that requires neuropeptide VIP signaling, yet the precise cellular mechanisms are unknown. Patton et al. show that cells expressing VIP or its receptor VPAC2 together determine these emergent properties of the SCN.
- Andrew P. Patton
- , Mathew D. Edwards
- & Michael H. Hastings
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Article
| Open AccessAstrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep
Despite evidence that astrocytes mediate sleep-dependent function, the involved signaling mechanisms are unknown. The authors show that astrocytic Ca2+ signalling exhibits distinct features across the sleep-wake cycle and ablation of this Ca2+ signalling pathway impairs slow wave sleep.
- Laura Bojarskaite
- , Daniel M. Bjørnstad
- & Erlend A. Nagelhus
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Article
| Open AccessRapid fast-delta decay following prolonged wakefulness marks a phase of wake-inertia in NREM sleep
Changes in EEG delta-activity are widely used as proxy of sleep propensity. Here the authors demonstrate in mice and humans the presence of two types of delta-waves, only one of which reports on prior sleep-wake history with dynamics denoting a wake-inertia process accompanying deepest non-rapid-eye-movement sleep (NREM) sleep.
- Jeffrey Hubbard
- , Thomas C. Gent
- & Paul Franken
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Article
| Open AccessCircadian regulation of hedonic appetite in mice by clocks in dopaminergic neurons of the VTA
In addition to promoting overconsumption, palatable diets dampen daily intake patterns, which further augments metabolic dysfunction. Here, the authors find that in mice, circadian clocks in dopaminergic neurons in the ventral tegmental area drive hedonic appetite rhythms.
- C. E. Koch
- , K. Begemann
- & H. Oster
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Article
| Open AccessRole of serotonergic dorsal raphe neurons in hypercapnia-induced arousals
Dorsal raphe 5HT(DRSert) neurons regulate arousal from hypercapnia by their projections to the neurons in the external lateral parabrachial nucleus (PBel) that are glutamatergic and also express calcitonin gene related peptide (PBelCGRP). The DRSert input to the PBel modulates the arousal system to rising levels of blood CO2, and may be mediated by 5HT2a receptors on the PBelCGRP neurons.
- Satvinder Kaur
- , Roberto De Luca
- & Clifford B. Saper
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Article
| Open AccessPrecise coupling of the thalamic head-direction system to hippocampal ripples
Thalamic head direction (HD) cells are necessary to establish spatial maps in the hippocampus. Here, the authors show that HD cells tuned to a particular direction are coupled to individual hippocampal ripple events during sleep, suggesting an influence of the replay of specific trajectories during sleep memory consolidation.
- Guillaume Viejo
- & Adrien Peyrache
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Article
| Open AccessOutput from VIP cells of the mammalian central clock regulates daily physiological rhythms
VIP-expressing neurons play a central role in circadian timekeeping within the mammalian central clock. Here the authors use opto- and chemogenetic approaches to show that VIP neuronal activity regulates rhythmic activity in downstream hypothalamic target neurons and their physiological functions.
- Sarika Paul
- , Lydia Hanna
- & Timothy M. Brown
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Article
| Open AccessInsights into the aetiology of snoring from observational and genetic investigations in the UK Biobank
Snoring is common in the population and tends to be more prevalent in older and/or male individuals. Here, the authors perform GWAS for habitual snoring, identify 41 genomic loci and explore potential causal relationships with anthropometric and cardiometabolic disease traits.
- Adrián I. Campos
- , Luis M. García-Marín
- & Miguel E. Rentería
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Article
| Open AccessNeurons in the Nucleus papilio contribute to the control of eye movements during REM sleep
Rapid eye movement (REM) sleep is a sleep phase characterised by random eye movements for which the underlying motor commands are yet to be revealed. The authors describe that a cluster of medulla oblongata neurons in the Nucleus papiliocontributes to the control of eye movements during REM sleep.
- C. Gutierrez Herrera
- , F. Girard
- & M. R. Celio
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Article
| Open AccessMulti-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration
Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.
- Raymond Noordam
- , Maxime M. Bos
- & Susan Redline
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Article
| Open AccessA microfluidic-induced C. elegans sleep state
C. elegans sleep can be used to model neural state transitions. Here the authors show that adult C. elegans show quiescent sleep-like behavior when in a microfluidic chamber, and that this is regulated by temperature, mechanosensation and satiety.
- Daniel L. Gonzales
- , Jasmine Zhou
- & Jacob T. Robinson
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Article
| Open AccessGenome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes
A main symptom of chronic insufficient sleep is excessive daytime sleepiness. Here, Wang et al. report 42 genome-wide significant loci for self-reported daytime sleepiness in 452,071 individuals from the UK Biobank that cluster into two biological subtypes of either sleep propensity or sleep fragmentation.
- Heming Wang
- , Jacqueline M. Lane
- & Richa Saxena
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Article
| Open AccessDiurnal rhythms in gene expression in the prefrontal cortex in schizophrenia
Sleep disturbance is common in psychiatric disease, and this may contribute to altered circadian rhythm in gene expression. Here the authors show that rhythms in gene expression in the dorsolateral prefrontal cortex in schizophrenia are different to that seen in healthy controls.
- Marianne L. Seney
- , Kelly Cahill
- & Colleen A. McClung
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Article
| Open AccessBidirectional prefrontal-hippocampal dynamics organize information transfer during sleep in humans
How are memories transferred from short-term to long-term storage? Here, the authors show that during deep (NREM) sleep, the prefrontal cortex initiates rapid, bidirectional interactions to trigger information transfer from the hippocampus to the neocortex.
- Randolph F. Helfrich
- , Janna D. Lendner
- & Robert T. Knight
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Article
| Open AccessActivating an anterior nucleus gigantocellularis subpopulation triggers emergence from pharmacologically-induced coma in rodents
The reticular activating system (RAS) of the brainstem regulates wakefulness, and stimulation of RAS areas can reverse effects of anaesthesia. Here, the authors show that stimulation of a particular RAS area, the anterior portion of nucleus gigantocellularis, can produce arousal from deep coma.
- S. Gao
- , A. Proekt
- & D. W. Pfaff
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Article
| Open AccessLarge-scale brain modes reorganize between infant sleep states and carry prognostic information for preterms
Patterns of brain activity during sleep in early stages of life influence brain development and behavior. Here, the authors reveal cortical dynamics underpinning quiet and active sleep states in pre- and full-term infants, and their links to neurodevelopmental outcomes.
- Anton Tokariev
- , James A. Roberts
- & Luca Cocchi
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Article
| Open AccessNREM sleep in the rodent neocortex and hippocampus reflects excitable dynamics
NREM sleep in rodents is characterized by internal dynamics in the form of UP/DOWN states in the neocortex and SWRs in the hippocampus. Here, the authors report that a mean field model with excitable dynamics captures the transition probabilities between these states from rodent sleep data.
- Daniel Levenstein
- , György Buzsáki
- & John Rinzel
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Article
| Open AccessGenetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour
Quality, quantity and timing of sleep are important factors for overall human health. Here, the authors perform GWAS for sleep traits estimated using wearable accelerometers and identify 47 genetic associations, including 26 novel associations for measures of sleep quality and 10 for nocturnal sleep duration.
- Samuel E. Jones
- , Vincent T. van Hees
- & Andrew R. Wood
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Article
| Open AccessSleep increases chromosome dynamics to enable reduction of accumulating DNA damage in single neurons
Do single neurons require sleep and what is the conserved cellular function of sleep? In this paper, the authors use real-time imaging of chromosomes in individual cells within live zebrafish to show that sleep increases chromosome dynamics, which are necessary to reduce DNA damage that is accumulated during wakefulness.
- D. Zada
- , I. Bronshtein
- & L. Appelbaum