ArticleNature communications2022
Orexin neurons inhibit sleep to promote arousal.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 3 of them syntheses that pooled it.
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
75 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Effects of non-pharmacological interventions on sleep in patients with critical illness: a systematic review and network meta-analysis.Scientific reports · 2026Pooled it
- Effectiveness of different repetitive transcranial magnetic stimulation modalities on sleep function and depression in patients with post-stroke sleep disorders: a systematic review and network meta-analysis of randomized controlled trials.Frontiers in neurology · 2025Pooled it
- Prevalence of post-stroke poor sleep quality: a meta-analysis of Pittsburgh Sleep Quality Index results.Frontiers in neurology · 2025Pooled it
- Effect of the orexin receptor antagonist, suvorexant, on sleep architecture in the early postoperative period following cardiac surgery: a randomized controlled trial.Critical care (London, England) · 2026Trial
- Trial
- Review
- Temporal profile of serum orexin-A in neonatal hypoxic-ischemic encephalopathy: a prospective longitudinal study.BMC pediatrics · 2026Observational
- Review
- The sleep-wake cycle: molecular mechanisms, disorders, and therapeutic targets in the context of energy metabolism.Signal transduction and targeted therapy · 2026Review
- Sleep circuit modulation: from animal models to human translation.Brain : a journal of neurology · 2026Review
- Oxytocin promotes socially triggered cataplexy.Nature neuroscience · 2026Article
- Overnight Dynamics of Ventricular Cerebrospinal Fluid Amyloid-Beta, Lactate and Hypocretin in Patients With Hydrocephalus: A Pilot Study.Journal of sleep research · 2026Observational
- Article
- Efferent projections of topographically distinct relaxin family peptide receptor-3 (RXFP3) lateral hypothalamus/zona incerta cells.Brain structure & function · 2026Article
- A gradual and sustainable approach to diagnosing sleep and circadian disturbances in dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Hypothalamic control of arousal.Reviews in endocrine & metabolic disorders · 2026Review
- Sleep regulates drug seeking and relapse - a perspective.Molecular psychiatry · 2026Review
- Dexamethasone induces sleep disruption in male mice and is associated with hyperactivation of orexin neurons.Psychopharmacology · 2026Article
- A hypothalamic circuit for circadian regulation of corticosterone secretion.Nature communications · 2026Article
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.
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Registered trials
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.