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| Open AccessVasoactive intestinal peptide controls the suprachiasmatic circadian clock network via ERK1/2 and DUSP4 signalling
The suprachiasmatic nucleus (SCN) synchronises daily rhythms of behaviour and physiology to the light-dark cycle. Vasoactive intestinal peptide (VIP) is important for mediating SCN entrainment; however, the underlying mechanisms are incompletely understood. Here, the authors show that the effects of VIP on the SCN are mediated by ERK1/2 and DUSP4.
- Ryan Hamnett
- , Priya Crosby
- & Michael H. Hastings
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| Open AccessGenome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms
GWAS have previously found 24 genomic loci associated with chronotype, an individual’s preference for early or late sleep timing. Here, the authors identify 327 additional loci in a sample of 697,828 individuals and further explore the relationships of chronotype with metabolic and psychiatric diseases.
- Samuel E. Jones
- , Jacqueline M. Lane
- & Michael N. Weedon
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| Open AccessThe HisCl1 histamine receptor acts in photoreceptors to synchronize Drosophila behavioral rhythms with light-dark cycles
The role of the HisCl1 histamine receptor in the Drosophila visual system remains unclear. This study shows that HisCl1 is expressed in Rh6-photoreceptors where its function is sufficient for circadian entrainment by incorporating synaptic inputs from other photoreceptors.
- Faredin Alejevski
- , Alexandra Saint-Charles
- & François Rouyer
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| Open AccessLocal hippocampal fast gamma rhythms precede brain-wide hyperemic patterns during spontaneous rodent REM sleep
Neural activity during REM sleep is similar to the waking state. Here, the authors measure blood volume with neurofunctional ultrasound imaging together with hippocampal neural activity during REM sleep and report that fast gamma oscillations are coupled to a brain-wide upregulation of vascular flow.
- Antoine Bergel
- , Thomas Deffieux
- & Ivan Cohen
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| Open AccessNeural network analysis of sleep stages enables efficient diagnosis of narcolepsy
The diagnosis of sleep disorders such as narcolepsy and insomnia currently requires experts to interpret sleep recordings (polysomnography). Here, the authors introduce a neural network analysis method for polysomnography that could reduce time spent in sleep clinics and automate narcolepsy diagnosis.
- Jens B. Stephansen
- , Alexander N. Olesen
- & Emmanuel Mignot
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| Open AccessIn vivo cell type-specific CRISPR knockdown of dopamine beta hydroxylase reduces locus coeruleus evoked wakefulness
Neurons of the locus coeruleus (LC) are implicated in attention and arousal. Here the authors use CRISPR/Cas9 to disrupt dopamine beta hydroxylase in LC neurons and see this reduces LC-evoked sleep-to-wake transitions and wake length.
- Hiroshi Yamaguchi
- , F. Woodward Hopf
- & Luis de Lecea
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| Open AccessSleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients
Many brain-injured patients retain large cortical islands that are intact, active and reactive but blocked in a state of low complexity, leading to unconsciousness. Here, the authors show that this loss of complexity is due to the pathological engagement of sleep-like neuronal mechanisms.
- M. Rosanova
- , M. Fecchio
- & M. Massimini
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| Open AccessHub-organized parallel circuits of central circadian pacemaker neurons for visual photoentrainment in Drosophila
The central circadian clock in Drosophila is made up of ~ 150 anatomically distributed neurons; the circuits underlying photoentrainment is unclear. This study describes ex vivo patch-clamp recording of the eye-mediated light response of all known circadian clock neurons, and shows that they are organized in parallel circuits centered around a hub.
- Meng-Tong Li
- , Li-Hui Cao
- & Dong-Gen Luo
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Article
| Open AccessGalanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice
Anatomical lesions of the preoptic area (POA) can cause sleep loss while electrical, chemical, or thermal stimulation of POA can induce sleep. To better understand the exact neural function of the POA, this study shows that galanin and GABA+ inhibitory neurons in the ventrolateral POA that project to the wake-promoting tuberomammillary nucleus promote sleep in a stimulation frequency dependent manner.
- Daniel Kroeger
- , Gianna Absi
- & Ramalingam Vetrivelan
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| Open AccessHuman hippocampal replay during rest prioritizes weakly learned information and predicts memory performance
The hippocampus is known to 'replay' experiences and memories during rest periods, but it is unclear how particular memories are prioritized for replay. Here, the authors show that information that is remembered less well is replayed more often, suggesting that weaker memories are selected for replay.
- Anna C. Schapiro
- , Elizabeth A. McDevitt
- & Kenneth A. Norman
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Article
| Open AccessEpigenetic regulation of the circadian gene Per1 contributes to age-related changes in hippocampal memory
Circadian rhythms are known to modulate memory, but it’s not known whether clock genes in the hippocampus are required for memory consolidation. Here, the authors show that epigenetic regulation of clock gene Period1 in the hippocampus regulates memory and contributes to age-related memory decline, independent of circadian rhythms.
- Janine L. Kwapis
- , Yasaman Alaghband
- & Marcelo A. Wood
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| Open AccessSmooth tracking of visual targets distinguishes lucid REM sleep dreaming and waking perception from imagination
When tracking a moving object, our eyes make smooth pursuit movements; however, tracking an imaginary object produces jerky saccadic eye movements. Here, the authors show that during lucid dreams, the eyes smoothly follow dreamed objects. In this respect, dream imagery is more similar to perception than imagination.
- Stephen LaBerge
- , Benjamin Baird
- & Philip G. Zimbardo
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Article
| Open AccessSleep loss causes social withdrawal and loneliness
Loneliness markedly increases mortality and morbidity, yet the factors triggering loneliness remain largely unknown. This study shows that sleep loss leads to a neurobehavioral phenotype of human social separation and loneliness, one that is transmittable to non-sleep-deprived individuals.
- Eti Ben Simon
- & Matthew P. Walker
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| Open AccessSleep-dependent reconsolidation after memory destabilization in starlings
Sleep is important for memory consolidation but its role in reconsolidation is not known. Here, the authors show in starlings that an auditory memory consolidated by sleep can be destabilized by retrieval and impaired by subsequent interference, but the memory recovers and stabilizes after a night of sleep-dependent reconsolidation.
- Timothy P. Brawn
- , Howard C. Nusbaum
- & Daniel Margoliash
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| Open AccessRegulation of cortical activity and arousal by the matrix cells of the ventromedial thalamic nucleus
The ventromedial thalamus (VM) is thought to control cortical arousal through its diffuse projections to cortex. Here the authors record and manipulate the activity of calbindin1-positive matrix cells in VM and show that they bidirectionally regulate the sleep-wake transition.
- Sakiko Honjoh
- , Shuntaro Sasai
- & Chiara Cirelli
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| Open AccessSnord116-dependent diurnal rhythm of DNA methylation in mouse cortex
Many genes have oscillating gene expression pattern in circadian centers of the brain. This study shows cortical diurnal DNA methylation oscillation in a mouse model of Prader-Willi syndrome, and describes corresponding changes in gene expression and chromatin compaction.
- Rochelle L. Coulson
- , Dag H. Yasui
- & Janine M. LaSalle
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| Open AccessNucleus accumbens controls wakefulness by a subpopulation of neurons expressing dopamine D1 receptors
The nucleus accumbens regulates many behaviours that depend on arousal. Here the authors show that dopamine D1 receptor neurons in the nucleus accumbens can directly regulate wakefulness.
- Yan-Jia Luo
- , Ya-Dong Li
- & Zhi-Li Huang
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Article
| Open AccessEndogenous modulation of human visual cortex activity improves perception at twilight
Visual perception depends on light—which changes according to time of day—but the accompanying neural changes are unknown. Here, authors use fMRI to describe the brain dynamics underlying visual perception and find that sensory areas change their activity to compensate for lower light at dawn and dusk.
- Lorenzo Cordani
- , Enzo Tagliazucchi
- & Christian A. Kell
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| Open AccessThe choroid plexus is an important circadian clock component
The suprachiasmatic nucleus (SCN) has been thought of as the master circadian clock, but peripheral circadian clocks do exist. Here, the authors show that the choroid plexus displays oscillations more robust than the SCN and that can be described as a Poincaré oscillator with negative twist.
- Jihwan Myung
- , Christoph Schmal
- & Toru Takumi
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| Open AccessVentromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder
Loss of muscle tone is a distinguishing feature of paradoxical or REM sleep (PS) and is disrupted in REM sleep behavior disorder. Here the authors report that GABA/glycine inhibitory neurons in the ventromedial medulla are essential for producing PS muscle atonia without affecting PS quantity.
- Sara Valencia Garcia
- , Frédéric Brischoux
- & Patrice Fort
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| Open AccessSubcortical evidence for a contribution of arousal to fMRI studies of brain activity
Resting cortical activity fluctuates, but it is unclear what underlies these variations in activity. Here, the authors show that large-scale fluctuations in fMRI cortical activity are associated with momentary decreases in cortical arousal and opposite activity changes in the basal forebrain and thalamus.
- Xiao Liu
- , Jacco A. de Zwart
- & Jeff H. Duyn
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| Open AccessSleeping sickness is a circadian disorder
African sleeping sickness is well known for the alterations of sleeping patterns, but it is not known how circadian biology is altered by the causative pathogen Trypanosoma brucei. Here the authors show T. brucei causes a disorder of the cellular circadian clock that is unrelated to the immune response to the parasite.
- Filipa Rijo-Ferreira
- , Tânia Carvalho
- & Joseph S. Takahashi
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| Open AccessLoss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease
Circadian controls of immune responses by the molecular clock have been reported, but the underlying mechanisms are unclear. Here the authors show that the master circadian gene, Bmal1, is essential for modulating the homeostasis of myeloid cells to control pro-inflammatory IL-17+/IFN-γ+ T cells in autoimmunity.
- Caroline E. Sutton
- , Conor M. Finlay
- & Annie M. Curtis
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| Open AccessAuditory closed-loop stimulation of EEG slow oscillations strengthens sleep and signs of its immune-supportive function
Circulating hormones undergo fluctuations during sleep. Here, the authors increase electroencephalographic slow oscillations (SO) during sleep in men using an auditory closed-loop stimulation, and show that the circulating level of cortisol, aldosterone and immune cell count can be altered.
- Luciana Besedovsky
- , Hong-Viet V. Ngo
- & Jan Born
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| Open AccessOscillatory brain activity in spontaneous and induced sleep stages in flies
Sleep in mammals comprises physiologically and functionally distinct stages. Here, the authors report a transitional sleep stage in Drosophila associated with 7–10 Hz oscillatory activity that can be obtained through activation of the sleep-promoting neurons of the dorsal fan-shaped body.
- Melvyn H. W. Yap
- , Martyna J. Grabowska
- & Bruno van Swinderen
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| Open AccessSupramammillary glutamate neurons are a key node of the arousal system
Supramammillary nucleus (SuM) neurons have been studied in the context of REM sleep but their possible role in mediating wakefulness is not known. Here the authors elucidate the distinct functional contributions of three subpopulations in the SuM on electrographical and behavioral arousal in mice using genetically targeted approaches.
- Nigel P. Pedersen
- , Loris Ferrari
- & Patrick M. Fuller
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| Open AccessLow frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings
Transcranial alternating current stimulation (tACS) has been proposed to enhance neural rhythms supporting memory. Here, the authors leverage human intracranial recordings to show that low-frequency tACS does not entrain key rhythms in non-REM sleep or resting wakefulness.
- Belen Lafon
- , Simon Henin
- & Anli A. Liu
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| Open AccessSlow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice
In addition to circadian and homoeostatic drives, motivational levels influence sleep−wake cycles. Here the authors demonstrate that adenosine receptor-expressing neurons in the nucleus accumbens core that project to the ventral pallidum are inhibited by motivational stimuli and are causally involved in the control of slow-wave sleep.
- Yo Oishi
- , Qi Xu
- & Michael Lazarus
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| Open AccessCortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents
Different stages of sleep, marked by particular electroencephalographic (EEG) signatures, have been linked to memory consolidation, but underlying mechanisms are poorly understood. Here, the authors show that dendritic calcium synchronisation correlates with spindle-rich sleep phases.
- Julie Seibt
- , Clément J. Richard
- & Matthew E. Larkum
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| Open AccessCortical Up states induce the selective weakening of subthreshold synaptic inputs
Slow oscillations between cortical Up and Down states are a defining feature of deep sleep, but their function is not well understood. Here the authors study Up/Down states in acute slices of entorhinal cortex, and find that Up states promote the weakening of subthreshold synaptic inputs, while suprathreshold inputs are preserved or strengthened.
- Julian Bartram
- , Martin C. Kahn
- & Edward O. Mann
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| Open AccessDynamic plasticity in phototransduction regulates seasonal changes in color perception
Animal coloration and behavior can change seasonally, but it is unclear if visual sensitivity to color shifts as well. Here, Shimmura et al. show that medaka undergo seasonal behavioral change accompanied by altered expression of opsin genes, resulting in reduced visual sensitivity to mates during winter-like conditions.
- Tsuyoshi Shimmura
- , Tomoya Nakayama
- & Takashi Yoshimura
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| Open AccessFormation and suppression of acoustic memories during human sleep
Though memory and sleep are related, it is still unclear whether new memories can be formed during sleep. Here, authors show that people could learn new sounds during REM or light non-REM sleep, but that learning was suppressed when sounds were played during deep NREM sleep.
- Thomas Andrillon
- , Daniel Pressnitzer
- & Sid Kouider
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Article
| Open AccessGenetic and neuronal mechanisms governing the sex-specific interaction between sleep and sexual behaviors in Drosophila
Genes and circuits involved in sleep and sexual arousal have been extensively studied in Drosophila. Here the authors identify the sex determination genes fruitless and doublesex, and a sex-specific P1-DN1 neuronal feedback that governs the interaction between these competing behaviors
- Dandan Chen
- , Divya Sitaraman
- & Yufeng Pan
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| Open AccessCharacterizing sleep spindles in 11,630 individuals from the National Sleep Research Resource
Sleep patterns vary and are associated with health and disease. Here Purcellet alcharacterize sleep spindle activity in 11,630 individuals and describe age-related changes, genetic influences, and possible confounding effects, serving as a resource for further understanding the physiology of sleep.
- S. M. Purcell
- , D. S. Manoach
- & R. Stickgold
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| Open AccessCentral and peripheral clocks are coupled by a neuropeptide pathway in Drosophila
The emergence of the adult fruit flies from the pupae is jointly regulated by the central and peripheral clocks. Selchoet al. show that synchronization of the two clocks is mediated by the master clock brain neurons producing sNPF, and non-clock PTTH neurons that regulate the peripheral clock producing the steroid moulting hormone, ecdysone.
- Mareike Selcho
- , Carola Millán
- & John Ewer
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| Open AccessCoordination of cortical and thalamic activity during non-REM sleep in humans
During non-REM sleep, the thalamus produces spindles and the cortex produces downstates, but the interaction between these two areas in these sleep phenomena is not understood. Here, authors describe the dynamic loop between the thalamus and cortex that organizes the production of spindles and downstates in the human brain.
- Rachel A. Mak-McCully
- , Matthieu Rolland
- & Eric Halgren
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| Open AccessDeep sleep maintains learning efficiency of the human brain
Deep sleep is hypothesized to restore the brain's capacity to learn. Here the authors provide causal evidence by specifically perturbing slow wave activity over the motor cortex during NREM sleep in humans and demonstrate a reduction in neurophysiological markers of plasticity and capacity for motor learning.
- Sara Fattinger
- , Toon T. de Beukelaar
- & Reto Huber
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| Open AccessDecoding material-specific memory reprocessing during sleep in humans
Neuronal learning activity is reactivated during sleep but the dynamics of this reactivation in humans are still poorly understood. Here the authors show that memory processing occurs during all stages of sleep in humans but that reprocessing of memory content in REM and non-REM sleep has different effects on later memory performance.
- M. Schönauer
- , S. Alizadeh
- & S. Gais
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| Open AccessParvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation
Episodic memory consolidation requires activity in hippocampal area CA1. Here the authors report that pharmacogenetic inhibition of CA1 PV+ interneuron firing after fear learning blocks memory consolidation and disrupts associated enhancement in network oscillations and stabilization of functional connectivity patterns.
- Nicolette Ognjanovski
- , Samantha Schaeffer
- & Sara J. Aton
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Article
| Open AccessDiurnal and seasonal molecular rhythms in human neocortex and their relation to Alzheimer’s disease
Diurnal and seasonal rhythms modulate brain function, but we do not know the genomic basis for these rhythms. Here, Limet al. show diurnal and seasonal rhythms of gene expression in the human brain, their relationship to histone acetylation and DNA methylation, and their disruption in Alzheimer’s disease.
- Andrew S. P. Lim
- , Hans-Ulrich Klein
- & Philip L. De Jager
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Article
| Open AccessMicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila
Accumulating evidence suggests that microRNAs play a role in circadian regulation. Here the authors show that in theDrosophila brain, mir-92a suppresses the excitability of PDF neurons—key circadian pacemaker cells in Drosophila—via inhibiting the translation of its target sirt2.
- Xiao Chen
- & Michael Rosbash
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Article
| Open AccessCircadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging
Disruption of circadian rhythms leads to reduced healthspan, but the mechanisms by which the normal clock protects aging organisms are not known. Here, the authors show that a subset of genes becomes more rhythmically expressed in older flies, and these are enriched for response to oxidative stress.
- Rachael C. Kuintzle
- , Eileen S. Chow
- & David A Hendrix
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Article
| Open AccessRegulation of persistent sodium currents by glycogen synthase kinase 3 encodes daily rhythms of neuronal excitability
It is not clear how circadian biochemical cascades are encoded into neural electrical signals. Here, using a combination of electrophysiology and modelling approaches in mice, the authors show activation of glycogen synthase kinase 3 modulates neural activity in the suprachiasmatic nuclei via regulation of the persistent sodium current, INaP.
- Jodi R. Paul
- , Daniel DeWoskin
- & Karen L. Gamble
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Article
| Open AccessStereotypic wheel running decreases cortical activity in mice
Sleep need is thought to accumulate gradually over waking periods and is associated with changes in neuronal activity. Here the authors show that in mice cortical firing rates increase between the beginning and end of wakefulness periods but this increase is not seen in waking periods with voluntary stereotypic wheel running.
- Simon P. Fisher
- , Nanyi Cui
- & Vladyslav V. Vyazovskiy
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Article
| Open AccessGlucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia
Neuropathic pain hypersensitivity is known to undergo diurnal variations, although the underlying mechanisms are not clear. Using a sciatic nerve-injury mouse model, the authors find such diurnal changes are mediated by glucocorticoid induced enhancement of ATP release from astrocytes via pannexin-1 hemichannels.
- Satoru Koyanagi
- , Naoki Kusunose
- & Shigehiro Ohdo
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Article
| Open AccessSCOP/PHLPP1β mediates circadian regulation of long-term recognition memory
Learning and memory are subject to circadian variation, though the molecular mechanisms behind this are unclear. Here, the authors show SCOP, a regulator of hippocampal memory, undergoes circadian changes in CA1 membrane raft dynamics and contributes to time-dependent changes in long-term memory.
- Kimiko Shimizu
- , Yodai Kobayashi
- & Yoshitaka Fukada
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| Open AccessSleep recalibrates homeostatic and associative synaptic plasticity in the human cortex
Sleep deprivation is believed to lead to homeostatic increases in synaptic strength and reduced inducibility of associative LTP, based mainly on findings from animal studies. Here, Kuhn et al. demonstrate similar sleep-dependent synaptic plasticity changes in humans along with altered plasma BDNF levels.
- Marion Kuhn
- , Elias Wolf
- & Christoph Nissen
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Article
| Open AccessEvidence that birds sleep in mid-flight
Whether and how birds sleep during long-distance flights has remained a mystery. Here, Rattenborg and colleagues show for the first time that frigatebirds can sleep during flight, but do so in remarkably small amounts.
- Niels C Rattenborg
- , Bryson Voirin
- & Alexei L. Vyssotski
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| Open AccessCircadian regulation of human cortical excitability
Cognitive performance is impaired after prolonged wakefulness, yet the contribution of circadian rhythms for proper brain function remains unclear. Here the authors show that cortical excitability measured using TMS exhibits robust circadian dynamics which is correlated with cognitive performance.
- Julien Q. M. Ly
- , Giulia Gaggioni
- & Gilles Vandewalle