ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Effects and neuroprotective mechanisms of vagus nerve stimulation on cognitive impairment with traumatic brain injury in animal studies: A systematic review and meta-analysis.Frontiers in neurology · 2022Pooled it
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Hypothalamic control of arousal.Reviews in endocrine & metabolic disorders · 2026Review
- Review
- Timed exercise modulates inter-coupling strength between evening and morning oscillators in mice.Npj biological timing and sleep · 2026Article
- Neuropeptidergic Input from the Lateral Hypothalamus to the Suprachiasmatic Nucleus Alters the Circadian Period in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Dual orexin receptor antagonists as promising therapeutics for Alzheimer's disease.Npj biological timing and sleep · 2025Review
- Loss of neuropeptide signalling alters temporal expression of mouse suprachiasmatic neuronal state and excitability.The European journal of neuroscience · 2024Article
- A novel developmental critical period of orexinergic signaling in the primary visual thalamus.iScience · 2024Article
- Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control.Molecular psychiatry · 2024Article
- AAV8-P301L tau expression confers age-related disruptions in sleep quantity and timing.Npj biological timing and sleep · 2024Article
- Diurnal Characteristics of the Orexin System Genes and Its Effects on Pathology at Early Stage in 3xTg-AD Mice.Neuromolecular medicine · 2023Article
- Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.Nature communications · 2023Article
- Physiological Role of Orexinergic System for Health.International journal of environmental research and public health · 2022Review
- Choroid plexus function in neurological homeostasis and disorders: The awakening of the circadian clocks and orexins.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Differences in recovery processes of circadian oscillators in various tissues after sevoflurane treatmentBiochemistry and biophysics reports · 2022Article
- Orexin 2 receptor (OX2R) protein distribution measured by autoradiography using radiolabeled OX2R-selective antagonist EMPA in rodent brain and peripheral tissues.Scientific reports · 2022Article
- Insulin-like Growth Factor I Couples Metabolism with Circadian Activity through Hypothalamic Orexin Neurons.International journal of molecular sciences · 2022Article
- Dual Orexin Receptor Antagonist Attenuates Increases in IOP, ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats.Investigative ophthalmology & visual science · 2022Article
- Multi-Level Processes and Retina-Brain Pathways of Photic Regulation of Mood.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX1 and OX2) in the mouse SCN, with OX1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K(+) currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain.
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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.