ArticleProceedings of the National Academy of Sciences of the United States of America2007
Control of hypothalamic orexin neurons by acid and CO2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02593682 (The Role of Orexin in Human Panic Disorder), which is not on this map. Cited by 145 papers.
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.
The Role of Orexin in Human Panic Disorder
Who cites it
145 citing papers in PubMed, 287 citations in OpenAlex.
- Neuroendocrine and sympathetic responses to an orexin receptor antagonist, SB-649868, and alprazolam following insulin-induced hypoglycemia in humans.Psychopharmacology · 2014Trial
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- Current and Developing Approaches for Facilitating Emergence from General Anesthesia.Anesthesiology · 2025Review
- Loss of M1 Acetylcholine Receptor-mediated Orexinergic Activity Contributes to Immune Dysfunction in Experimental Sepsis.Research square · 2025Article
- Alluring Potential to Accelerate Emergence and Ameliorate Opioid-induced Respiratory Depression without Antagonizing Analgesia: Danavorexton Enters the Anesthetic Landscape.Anesthesiology · 2025Article
- Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception.International journal of molecular sciences · 2025Review
- Altered ventilatory responses to hypercapnia-hypoxia challenges in a preclinical SUDEP model involve orexin neurons.Neurobiology of disease · 2024Article
- Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture.Nature communications · 2024Article
- Orexin neurons track temporal features of blood glucose in behaving mice.Nature neuroscience · 2024Article
- Interactions between Lateral Hypothalamic Orexin and Dorsal Raphe Circuitry in Energy Balance.Brain sciences · 2024Article
- Metabolic underpinnings of cancer-related fatigue.American journal of physiology. Endocrinology and metabolism · 2024Review
- Review
- Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups.Frontiers in physiology · 2023Review
- Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations.Nature and science of sleep · 2023Review
- Estrogens, age, and, neonatal stress: panic disorders and novel views on the contribution of non-medullary structures to respiratory control and COFrontiers in physiology · 2023Review
- COBMC psychiatry · 2022Article
- COBrain structure & function · 2022Article
- Orexin facilitates the ventilatory and behavioral responses of rats to hypoxia.American journal of physiology. Regulatory, integrative and comparative physiology · 2022Article
- Central respiratory chemoreception.Handbook of clinical neurology · 2022Review
- Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy.Frontiers in neurology · 2022Article
85 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 4 countries.
Funding
Abstract
Hypothalamic orexin/hypocretin neurons recently emerged as key orchestrators of brain states and adaptive behaviors. They are critical for normal stimulation of wakefulness and breathing: Orexin loss causes narcolepsy and compromises vital ventilatory adaptations. However, it is unclear how orexin neurons generate appropriate adjustments in their activity during changes in physiological circumstances. Extracellular levels of acid and CO2 are fundamental physicochemical signals controlling wakefulness and breathing, but their effects on the firing of orexin neurons are unknown. Here we show that the spontaneous firing rate of identified orexin neurons is profoundly affected by physiological fluctuations in ambient levels of H+ and CO2. These responses resemble those of known chemosensory neurons both qualitatively (acidification is excitatory, alkalinization is inhibitory) and quantitatively (approximately 100% change in firing rate per 0.1 unit change in pHe). Evoked firing of orexin cells is similarly modified by physiologically relevant changes in pHe: Acidification increases intrinsic excitability, whereas alkalinization depresses it. The effects of pHe involve acid-induced closure of leak-like K+ channels in the orexin cell membrane. These results suggest a new mechanism of how orexin/hypocretin networks generate homeostatically appropriate firing patterns.
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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.