ArticleScience (New York, N.Y.)2022
Hyperexcitable arousal circuits drive sleep instability during aging.
Open access · greenAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 1 pooled it
20.5field-weighted citation impact, top 1% of its field
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Sleep quality assessment in hospitalized postoperative surgical patients: a COSMIN-based systematic review.Frontiers in sleep · 2025Pooled it
- Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial.Drugs & aging · 2022Trial
- Corticotropin-releasing hormone neurons in the bed nucleus of the stria terminalis control wakefulness in physiological and stressful conditions in mice.Molecular psychiatry · 2026Article
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- Acupuncture modulates migraine-related neural and neuroendocrine regulatory pathways.The journal of headache and pain · 2026Review
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- Joint trajectories of sleep deviation risk and frailty and their associations with cognitive decline in middle-aged and older adults: a population-based cohort study.BMC public health · 2026Article
- Evidence for Potentiation of M-Type Potassium Current by Flavonoid Corylin (3-(2,2-Dimethylchromen-6-yl)-7-hydroxychromen-4-one).Pharmaceuticals (Basel, Switzerland) · 2026Article
- Sleep disturbances and Alzheimer's disease: a multiscale approach from exposome to neurobiology and precision medicine.GeroScience · 2026Review
- Article
- Molecular signatures of resilience to Alzheimer's disease in neocortical layer 4 neurons.Nature communications · 2026Article
- Social rank and social environment combinedly affect REM sleep in mice.Scientific reports · 2026Article
- BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.EMBO reports · 2026Article
- Serum hypocretin, neurofilament heavy chain, and interleukin-1β as combined predictors of sleep disorders following acute ischemic stroke.Frontiers in neuroscience · 2026Article
- Multimodal characterization of cortical hyperexcitability as a driver of cognitive decline in neurocognitive disorders: study protocol for the LENDÜLET Neurocognitive Research Project.Frontiers in aging neuroscience · 2026Article
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- Multi-Omics Analysis Reveals Nono-Kcnq2 Regulation of Neuronal Excitability in Chronic Constriction Injury-Induced Neuropathic Pain.Research (Washington, D.C.) · 2026Article
- Daridorexant and Insomnia in Clinical Practice: A Nominal Group Technique Consensus Study among Italian Sleep and Insomnia Experts.Current neuropharmacology · 2026Article
- Obstructive Sleep Apnea and Hypercoagulability: Combining Observational and Mendelian Randomization Analyses to Explore Causal Relationships.Nature and science of sleep · 2026Article
- Adolescent Insomnia Disorder - Problematic Internet Use Nexus: A Convergent Developmental Trajectory - Bridging Neuroimaging Biomarkers, Molecular Susceptibility, and Environmental-Neurocognitive Cascades.Psychology research and behavior management · 2026Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Shi-Bin Li *Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-5699-3035
Valentina Martinez Damonte *Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0003-2843-2414
Chong ChenDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0002-8420-1410
Gordon X WangDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-2707-7118
Justus M KebschullDepartment of Biology, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-4851-0267
Hiroshi YamaguchiDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0003-4323-1282
Wen-Jie BianDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-0426-1297
Carolin PurmannDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-7691-1615
Reenal PattniDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0003-4490-731X
Alexander Eckehart UrbanDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0001-9772-933X
Philippe MourrainDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-3674-4015
Julie A KauerDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-3362-1642
Grégory ScherrerDepartment of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.ORCID 0000-0002-1983-5126
Luis de LeceaDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 1201 Welch Road, Stanford, CA 94305, USA.ORCID 0000-0002-8921-5942
Neurosciences Institute · USStanford Medicine · USUniversity of North Carolina at Chapel Hill · USInserm · FRStanford University · US
Funding
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2MStanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI STEPHEN A BACCUS · 2017 to 2026
$8.0MWorking Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI GREICIUS, MICHAEL D · 2015 to 2019
$7.9MInhibitory Synaptic Transmission, Stress and Drugs of AbuseR01DA011289 · NIDA · STANFORD UNIVERSITY · PI KAUER, JULIE A. · 1997 to 2023
$6.8MNeuropeptide S and arousalR01MH128140 · NIMH · STANFORD UNIVERSITY · PI DE LECEA, LUIS · 2021 to 2025
$2.9MImpact of sleep-wake circuits on cortical synapse plasticity during motor learningR01NS104950 · NINDS · STANFORD UNIVERSITY · PI MOURRAIN, PHILIPPE · 2018 to 2022
$2.6MFunctional Heterogeneity of Hypocretin NeuronsR01MH116470 · NIMH · STANFORD UNIVERSITY · PI APPELBAUM, LIOR YOSEF, DE LECEA, LUIS · 2019 to 2023
$2.4MOptogenetic interrogation of sleep circuits during agingR01AG047671 · NIA · STANFORD UNIVERSITY · PI DE LECEA, LUIS, WYSS-CORAY, TONY · 2014 to 2018
$2.1MIdentification of cells and signaling mechanisms underlying opioid analgesia and side effectsR01DA044481 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SCHERRER, GREGORY · 2017 to 2021
$1.8MAmygdala mechanisms of pain aversionR01NS106301 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SCHERRER, GREGORY · 2018 to 2022
$1.3MNon-REM (NREM) on synapse plasticity and beta amyloid (aB) accumulation in mice: impact on aging and Alzheimer'sK01AG061230 · NIA · STANFORD UNIVERSITY · PI WANG, GORDON X · 2019 to 2021
$380kNEI NIH HHS P30 EY026877NHGRI NIH HHS P50 HG007735NIA NIH HHS K01 AG061230NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG047671NIDA NIH HHS R01 DA011289NIDA NIH HHS R01 DA044481NIMH NIH HHS R01 MH116470NIMH NIH HHS R01 MH128140NINDS NIH HHS R01 NS104950NINDS NIH HHS R01 NS106301
Abstract
Sleep quality declines with age; however, the underlying mechanisms remain elusive. We found that hyperexcitable hypocretin/orexin (Hcrt/OX) neurons drive sleep fragmentation during aging. In aged mice, Hcrt neurons exhibited more frequent neuronal activity epochs driving wake bouts, and optogenetic activation of Hcrt neurons elicited more prolonged wakefulness. Aged Hcrt neurons showed hyperexcitability with lower KCNQ2 expression and impaired M-current, mediated by KCNQ2/3 channels. Single-nucleus RNA-sequencing revealed adaptive changes to Hcrt neuron loss in the aging brain. Disruption of
Indexed as
AgingSleepWakefulnessAminopyridinesAnimalsCRISPR-Cas SystemsElectroencephalographyElectromyographyFemaleHypothalamic Area, LateralKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelMaleMiceNarcolepsyNerve Tissue ProteinsAminopyridinesflupirtineHcrt protein, mouseKCNQ2 Potassium ChannelKcnq2 protein, mouseKCNQ3 Potassium ChannelKcnq3 protein, mouseNerve Tissue ProteinsOrexins
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.