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Optochemical control of slow-wave sleep in the nucleus accumbens of male mice by a photoactivatable allosteric modulator of adenosine A2A receptors
The nucleus accumbens integrates sleep and motivation in mice. Here, the authors show sleep induction by increasing the activity of extracellular adenosine from astrocytes and neurons at A2A receptors with a photoactivatable allosteric modulator.
- Koustav Roy
- , Xuzhao Zhou
- & Michael Lazarus
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Article
| Open Access
Disordered clock protein interactions and charge blocks turn an hourglass into a persistent circadian oscillator
Many clock proteins contain intrinsically disordered regions, but how these regions mediate protein interactions is poorly understood. Here, the authors identify charge blocks within a disordered clock protein that regulate circadian timing.
- Meaghan S. Jankowski
- , Daniel Griffith
- & Jennifer M. Hurley
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Article
| Open Access
Dynamic encoding of temperature in the central circadian circuit coordinates physiological activities
The central circadian circuit’s role in integrating temperature changes is not fully understood. Here, the authors demonstrate that temperature-sensitive DN1a circadian neurons in the Drosophila brain bidirectionally influence downstream circadian neurons, regulating temperature-dependent physiological activities.
- Hailiang Li
- , Zhiyi Li
- & Fang Guo
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Article
| Open Access
A midbrain GABAergic circuit constrains wakefulness in a mouse model of stress
Neural circuit mechanisms underlying prevention of hyperarousal in acute stress conditions are not fully understood. Here authors show GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus constrain the increase of wakefulness to prevent hyperarousal in a mouse model of stress.
- Shuancheng Ren
- , Cai Zhang
- & Zhian Hu
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Article
| Open Access
Context memory formed in medial prefrontal cortex during infancy enhances learning in adulthood
Early life experience contributes to behaviour in later life. Here the authors show in rats, that the infant brain, during a critical period, forms lasting memories of the spatial context of experiences; in adulthood, these memories involving medial prefrontal cortex improve spatial abilities in similar contexts.
- María P. Contreras
- , Marta Mendez
- & Marion Inostroza
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Matters Arising
| Open AccessDaylight saving time and mortality—proceed with caution
- Elizabeth B. Klerman
- , Matthew D. Weaver
- & Karin G. Johnson
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Article
| Open Access
Respiration modulates sleep oscillations and memory reactivation in humans
The memory function of sleep relies on the coordination of slow oscillations and spindles. Here the authors show that respiration is associated with the emergence and interplay of these sleep rhythms, and that this coupling is linked to memory reactivation.
- Thomas Schreiner
- , Marit Petzka
- & Bernhard P. Staresina
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Article
| Open Access
Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner
Mammalian circadian clocks align with feeding and light cues. Here, the authors reveal a role for astrocytic insulin-dopaminergic signaling in sex-specific circadian behavior and energy balance regulation.
- Antía González-Vila
- , María Luengo-Mateos
- & Olga Barca-Mayo
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Article
| Open Access
Opposing brain signatures of sleep in task-based and resting-state conditions
The associations between sleep, depression and brain activity are not well understood. Here, the authors show patterns of brain activity associated with insomnia and depression resemble those found in people who sleep less, but only under cognitive load. At rest, these activation patterns are hyperconnected and resemble those found in longer sleepers.
- Mohamed Abdelhack
- , Peter Zhukovsky
- & Daniel Felsky
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Article
| Open Access
Wake slow waves in focal human epilepsy impact network activity and cognition
Slow waves in sleep are crucial for homeostatic regulation of brain function. Here the authors show similar slow wave activity occurs during wakefulness in people with epilepsy to counter the impact of abnormal, epileptic, brain activity.
- Laurent Sheybani
- , Umesh Vivekananda
- & Matthew C. Walker
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Article
| Open Access
Spatial transcriptomics reveals unique gene expression changes in different brain regions after sleep deprivation
Sleep deprivation impacts molecular changes across brain regions. Here, the authors utilize a spatial. transcriptomics approach to elucidate acute sleep deprivation-induced gene expression signature. across regions and subregions of the brain.
- Yann Vanrobaeys
- , Zeru J. Peterson
- & Ted Abel
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Article
| Open Access
Diurnal oscillations of MRI metrics in the brains of male participants
Whether temporal variations in brain MRI metrics can be attributed to circadian or diurnal oscillations is unclear. Here, the authors show evidence for diurnal oscillations in MRI metrics in both healthy controls and participants with bipolar disorder.
- Matthew Carlucci
- , Tristram Lett
- & Art Petronis
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Article
| Open Access
Neuronal connected burst cascades bridge macroscale adaptive signatures across arousal states
Here the authors describe a biophysical layer-5 pyramidal neuronal model linking microscale spiking to macroscale complex dynamics, that predicts distinct burst dynamics and information processing across unconscious, dreaming, and awake states.
- Brandon R. Munn
- , Eli J. Müller
- & James M. Shine
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Article
| Open Access
The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption
Generalized body pain and headaches are common experience after sleep disruption. How does sleep disruption lead to generalized pain is unknown. Here, authors reveal that N-arachidonoyl dopamine, an endocannabinoid, is critically implicated in pain perception after sleep disruption.
- Weihua Ding
- , Liuyue Yang
- & Shiqian Shen
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Article
| Open Access
A clock-dependent brake for rhythmic arousal in the dorsomedial hypothalamus
How the circadian clock generates rhythms of arousal remains unclear. Here, authors show that a clock-output molecule reduces excitability of an arousal circuit during the active phase. These results suggest a multifaceted role for the clock in arousal.
- Qiang Liu
- , Benjamin J. Bell
- & Mark N. Wu
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Article
| Open Access
Circadian clock disruption promotes the degeneration of dopaminergic neurons in male Drosophila
Circadian disruptions are frequent comorbidities of neurodegenerative disorders, such as Parkinson’s, marked by dopaminergic neuron loss. Here, the authors reveal circadian clocks dictate the susceptibility of dopamine neurons to oxidative stress.
- Michaëla Majcin Dorcikova
- , Lou C. Duret
- & Emi Nagoshi
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Article
| Open Access
Pathological pallidal beta activity in Parkinson’s disease is sustained during sleep and associated with sleep disturbance
Sleep disturbances are highly prevalent in patients with Parkinson’s disease. Here, the authors leverage intracranial recordings in such patients, finding that pathological pallidal activity is present during sleep and associated with sleep disturbance.
- Zixiao Yin
- , Ruoyu Ma
- & Jianguo Zhang
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Article
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Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy in male mice
The circadian clock protein REV-ERBα has been implicated in neuroinflammation but mechanisms are poorly understood. Here, the authors show that microglial REV-ERBα regulates inflammatory signaling and lipid droplet formation to exert sex-specific effects on tau pathology in mice.
- Jiyeon Lee
- , Julie M. Dimitry
- & Erik S. Musiek
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Article
| Open Access
Circadian clock regulator Bmal1 gates axon regeneration via Tet3 epigenetics in mouse sensory neurons
Injured peripheral neurons activate pro-growth gene programs, yet the mechanisms remain unclear. Here, the authors show that disruption of circadian clock factor Bmal1 accelerates axon regeneration through augmented epigenetic responses after injury.
- Dalia Halawani
- , Yiqun Wang
- & Hongyan Zou
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Article
| Open Access
A brainstem to circadian system circuit links Tau pathology to sundowning-related disturbances in an Alzheimer’s disease mouse model
Sundowning in Alzheimer’s disease (AD) patients is characterized by agitation and aggression during their afternoon-to-evening transition and a phase delay in circadian rhythms. Here, the authors show that AD model mice develop a phase delay and increased aggression around their active-to-rest transition with Tau pathology in brainstem neurons that target the circadian system.
- Andrew E. Warfield
- , Pooja Gupta
- & William D. Todd
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Article
| Open Access
A common neuronal ensemble in nucleus accumbens regulates pain-like behaviour and sleep
A comorbidity of chronic pain is sleep disturbance. Here, authors show the identification and characterization of a common neuronal ensemble in NAc that regulates pain-like behaviour and sleep through its divergent downstream circuit targets.
- Haiyan Sun
- , Zhilin Li
- & Jun-Li Cao
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Article
| Open Access
Hearing of malaria mosquitoes is modulated by a beta-adrenergic-like octopamine receptor which serves as insecticide target
Malaria mosquitoes use their ears to detect the flight tones of mating partners in the swarm as part of the courtship ritual. Here, the authors describe the auditory role of octopamine as a modulator of auditory plasticity in malaria mosquitoes and identify the main receptors involved in this process.
- Marcos Georgiades
- , Alexandros Alampounti
- & Marta Andrés
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A medullary hub for controlling REM sleep and pontine waves
Pontine waves are a hallmark of REM sleep. Here, the authors identify a distinct population of medullary neurons that constitute a hub in the REM sleep circuitry promoting REM sleep with an enhanced density of pontine waves.
- Amanda L. Schott
- , Justin Baik
- & Franz Weber
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Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution
The choroid plexus (ChP) modulates cerebrospinal fluid (CSF) composition and the blood-CSF barrier. Here the authors show that the ChP is a critical circadian component with time-of-day variations in translation, barrier, and metabolism to alter CSF composition.
- Ryann M. Fame
- , Peter N. Kalugin
- & Maria K. Lehtinen
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Article
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Wide-spread brain activation and reduced CSF flow during avian REM sleep
Non-rapid eye movement (NREM) sleep is associated with increased cerebrospinal fluid (CSF) flow in mammals, but this link has not been studied in birds. Here, the authors show that in pigeons, REM sleep is associated with activation of visual brain regions and a drop in CSF flow, suggesting that REM sleep functions occur at the expense of waste clearance during NREM sleep.
- Gianina Ungurean
- , Mehdi Behroozi
- & Niels C. Rattenborg
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Article
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Circadian regulation of developmental synaptogenesis via the hypocretinergic system
Whether the circadian clock regulates early developmental processes is poorly understood. Here, the authors report the circadian rhythm of synapse formation during early brain development by using the retinotectal system of larval zebrafish as an in vivo model.
- Xu-Fei Du
- , Fu-Ning Li
- & Jiu-Lin Du
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Article
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Allnighter pseudokinase-mediated feedback links proteostasis and sleep in Drosophila
For homeostatic plasticity, neuronal circuits rely on poorly understood retrograde signals. Here, the authors identify a visual activity-dependent feedback loop mediated by the secreted Allnighter pseudokinase with effects on brain-wide proteostasis and sleep.
- Shashank Shekhar
- , Andrew T. Moehlman
- & Helmut Krämer
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Article
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Spectro-spatial features in distributed human intracranial activity proactively encode peripheral metabolic activity
How human brain activity relates to peripheral metabolism is not known. Here, the authors find that intracranial activity is strongly coupled to peripheral glucose variations across multiple brain regions and is sufficient for decoding of glucose levels.
- Yuhao Huang
- , Jeffrey B. Wang
- & Casey H. Halpern
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Article
| Open Access
Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice
The neural circuits regulating wakefulness have not been fully resolved. Here, the authors reveal that neurons expressing calretinin in the parasubthalamic nucleus play a key role in the induction and maintenance of the awake state associated with exploration via projections to the ventral tegmental area.
- Han Guo
- , Jian-Bo Jiang
- & Wei-Min Qu
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Article
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Distinct astrocytic modulatory roles in sensory transmission during sleep, wakefulness, and arousal states in freely moving mice
The contribution of astrocytic Ca2+ signaling to the modulation of sensory transmission in different brain states remains largely unknown. Here, the authors show two types of Ca2+ signals in the mouse barrel cortex with distinct function in sensory transmission during sleep and arousal states.
- Fushun Wang
- , Wei Wang
- & Jason H. Huang
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Article
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Circulating blood eNAMPT drives the circadian rhythms in locomotor activity and energy expenditure
Nicotinamide phosphoribosyl transferase (NAMPT) is a critical regulator of cellular nicotinamide adenine dinucleotide (NAD)+ levels. Here, the authors show that blood NAMPT contributes to the circadian rhythm generation of locomotor activity and energy expenditure by regulating hypothalamic NAD+ levels.
- Jae Woo Park
- , Eun Roh
- & Min-Seon Kim
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Article
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Time-of-day defines NAD+ efficacy to treat diet-induced metabolic disease by synchronizing the hepatic clock in mice
The timing of NAD + supply determines its efficacy to treat metabolic disease. Here, the authors show that increasing NAD + at the early active phase maximizes weight loss and glucose regulation in mice. NAD + can displace the phase of the liver clock which can cause circadian misalignment.
- Quetzalcoatl Escalante-Covarrubias
- , Lucía Mendoza-Viveros
- & Lorena Aguilar-Arnal
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Article
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Sleep fMRI with simultaneous electrophysiology at 9.4 T in male mice
Mechanisms of sleep remain elusive. Here, authors developed mouse sleep fMRI based on simultaneous electrophysiology and mapped global and sequential state transition patterns, together with global patterns triggered by SWRs in NREM and awake states.
- Yalin Yu
- , Yue Qiu
- & Zhifeng Liang
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Article
| Open Access
Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport
Why fluid and solute transport in perivascular spaces is enhanced upon sleep remains elusive. Here, the authors show that each sleep cycle state displays unique perivascular dynamics, which enhances predicted fluid movement and solute transport.
- Laura Bojarskaite
- , Alexandra Vallet
- & Rune Enger
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Article
| Open Access
SREBP modulates the NADP+/NADPH cycle to control night sleep in Drosophila
Mechanisms underlying sleep dysfunctions in neurodevelopmental disorders remain elusive. Here, authors use a fly model for the CYFIP haploinsufficiency to show that increased SREBP activity impairs the NADP+/NADPH homeostasis inducing sleep deficits.
- Vittoria Mariano
- , Alexandros K. Kanellopoulos
- & Claudia Bagni
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Memory for nonadjacent dependencies in the first year of life and its relation to sleep
Grammar learning requires memory for temporally organised, rule-based patterns in speech. Here, the authors use event-related potentials to show that 6 to 8 month-old infants can form memory of dependencies between nonadjacent elements in sentences of an unknown language, regardless of whether they nap or stay awake after encoding.
- Manuela Friedrich
- , Matthias Mölle
- & Angela D. Friederici
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Sleep-like unsupervised replay reduces catastrophic forgetting in artificial neural networks
Artificial neural networks are known to perform well on recently learned tasks, at the same time forgetting previously learned ones. The authors propose an unsupervised sleep replay algorithm to recover old tasks synaptic connectivity that may have been damaged after new task training.
- Timothy Tadros
- , Giri P. Krishnan
- & Maxim Bazhenov
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Article
| Open Access
Reported sleep duration reveals segmentation of the adult life-course into three phases
Sleep varies within and between individuals. Here, using self-reported sleep duration from a large sample of participants across 63 countries, the authors show three phases in the adult human life-course, consistent across culture, gender, education and other demographics.
- A. Coutrot
- , A. S. Lazar
- & H. J. Spiers
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Article
| Open Access
GABAergic neurons in the rostromedial tegmental nucleus are essential for rapid eye movement sleep suppression
The neural circuits regulating REM sleep are poorly understood. The authors reveal that GABAergic neurons in the rostromedial tegmental nucleus suppress the onset and maintenance of REM sleep, and that projections of these neurons to the LDT and LH mediate distinct REM sleep transitions.
- Ya-Nan Zhao
- , Jian-Bo Jiang
- & Su-Rong Yang
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How people wake up is associated with previous night’s sleep together with physical activity and food intake
In a prospective longitudinal study of 833 adults, we demonstrate that how you wake up and regain alertness in the hours after sleep is weakly associated with your genes. Instead, the modifiable factors of how you are sleeping, eating and exercising influence your return to full alertness, free of sleepiness.
- Raphael Vallat
- , Sarah E. Berry
- & Matthew P. Walker
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Article
| Open Access
REM sleep is associated with distinct global cortical dynamics and controlled by occipital cortex
The cortex is very active during sleep. Wang et al. used macroscopic Ca2+ imaging to record the global cortical activity from the entire dorsal cortex of mice during sleep and uncover an unexpected role of the cortex in controlling REM sleep.
- Ziyue Wang
- , Xiang Fei
- & Min Xu
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Article
| Open Access
Sleep decreases neuronal activity control of microglial dynamics in mice
Microglia survey the parenchyma, which leads to morphology changes over time. Here the authors show using 2 photon imaging of microglia in vivo that sleep modulates microglial morphodynamics through Cx3cr1 signaling.
- I. Hristovska
- , M. Robert
- & O. Pascual
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Article
| Open Access
A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice
The psychostimulant-sensitive neural mechanism linking the circadian clock to locomotion is unknown. Here, hypothalamic A14 neurons are shown to time diurnal activity by entraining the lateral septum, and their activity is shown to be sensitive to amphetamine.
- Solomiia Korchynska
- , Patrick Rebernik
- & Roman A. Romanov
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Article
| Open Access
A temporal sequence of thalamic activity unfolds at transitions in behavioral arousal state
How the brain transitions between sleep and wakefulness is not well understood. Here, the authors discover that a sequence of activity unfolds across the thalamus before transitions from unresponsiveness to active behavior.
- Beverly Setzer
- , Nina E. Fultz
- & Laura D. Lewis
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Article
| Open Access
The human thalamus orchestrates neocortical oscillations during NREM sleep
Slow oscillations, which are instrumental to memory consolidation, have been assumed to be solely generated in neocortex. Here, the authors show that the anterior thalamus might play a fundamental role in organizing slow oscillations in human sleep.
- Thomas Schreiner
- , Elisabeth Kaufmann
- & Tobias Staudigl
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Article
| Open Access
Control of non-REM sleep by ventrolateral medulla glutamatergic neurons projecting to the preoptic area
In this study, Teng et al. identify a population of glutamatergic neurons in the ventrolateral medulla that control Non-Rapid Eye Movement (NREM) sleep in mice. They uncover an excitatory brainstem-hypothalamic circuit that controls wake-sleep transitions.
- Sasa Teng
- , Fenghua Zhen
- & Yueqing Peng
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Article
| Open Access
Orexin neurons inhibit sleep to promote arousal
Sleep and wakefulness is stabilized by a population of orexin-expressing neurons. In this study, the authors demonstrate how these neurons drive arousal by silencing sleep-promoting neurons in the ventrolateral preoptic nucleus.
- Roberto De Luca
- , Stefano Nardone
- & Elda Arrigoni
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Article
| Open Access
Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster
Circadian dysfunction is a potential driver of eye aging. Here the authors report that in conjunction with the core molecular clock transcription factor Clock, dietary restriction promotes rhythmic homeostatic mechanisms within photoreceptors to delay visual senescence and extend lifespan in Drosophila Melanogaster.
- Brian A. Hodge
- , Geoffrey T. Meyerhof
- & Pankaj Kapahi
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Article
| Open Access
Knockdown 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
Large-language models facilitate discovery of the molecular signatures regulating sleep and activity