ArticleProceedings of the National Academy of Sciences of the United States of America2023
Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- Temporal drift of sleep-wake representations in hypothalamic neuronal ensembles.Nature communications · 2026Article
- Dual hypocretin receptor antagonists enhance sleep and nursing behavior in lactating rats.Psychopharmacology · 2026Article
- Rapid Eye Movement Sleep-Related Indicators with Promising Performance in Diagnosing Narcolepsy.Nature and science of sleep · 2026Article
- Polysomnographic Characteristics and Sleep Disorders in Pediatric Moyamoya Arteriopathy.Nature and science of sleep · 2026Article
- Narcolepsy: immunity, neural circuitry, and brain network reconfiguration.Frontiers in immunology · 2026Review
- Narcolepsy as an immune-associated hypothalamic encephalopathy: orexin dysfunction and implications for precision sleep medicine.Frontiers in psychiatry · 2026Review
- Orexin Deficiency in Narcolepsy: Molecular Mechanisms, Clinical Phenotypes, and Emerging Therapeutic Frontiers.Brain and behavior · 2025Review
- Orexinergic projections to substantia innominata mediate arousal and analgesia.British journal of anaesthesia · 2025Article
- Corticotropin-releasing hormone modulates NREM sleep consolidation through the thalamic reticular nucleus.Nature communications · 2025Article
- Narcolepsy and rapid eye movement sleep.Journal of sleep research · 2025Review
- The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection.The journal of physiological sciences : JPS · 2025Review
- Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus.Experimental neurology · 2025Article
- REM Density, Leg Movements, and REM Sleep without Atonia: Differentiating Type 1 from Type 2 Narcolepsy Through Polysomnographic Analysis, a Preliminary Study.Nature and science of sleep · 2025Article
- Hypocretin: a promising target for the regulation of homeostasis.Frontiers in neuroscience · 2025Review
- Serum Metabolomic Signatures of Dyslipidemia in Narcolepsy Type 1: A Multi-Center Cross-Sectional Study.Nature and science of sleep · 2025Article
- Bibliometric and visual study of narcolepsy from 2000 to 2023.World journal of psychiatry · 2024Article
- Spatial mRNA expression patterns of orexin receptors in the dorsal hippocampus.Scientific reports · 2024Article
- A male-specific mechanism of meningeal nociceptor sensitization promoting migraine headache.Cephalalgia : an international journal of headache · 2024Article
- Article
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Authors and funding
8 authors at 4 institutions in 3 countries.
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Abstract
Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.
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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.