ReviewJournal of applied physiology (Bethesda, Md. : 1985)2008
The 2008 Carl Ludwig Lecture: retrotrapezoid nucleus, CO2 homeostasis, and breathing automaticity.
Review in Journal of applied physiology (Bethesda, Md. : 1985), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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.
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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
85 citing papers in PubMed, 150 citations in OpenAlex.
- Carfentanil Depresses Inspiratory Motor Drive.Journal of substance abuse and alcoholism · 2026Article
- Effects of Intravenous Bolus Injection of Fentanyl on Phrenic Nerve Activity and Its Response to Hypoxia and Hypercapnia.Journal of pharmacy and pharmacology research · 2026Article
- The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in the Nervous System.Current neuropharmacology · 2024Review
- Hypercapnic signaling influences hypoxic signaling in the control of breathing in C57BL6 mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Carotid sinus nerve transection abolishes the facilitation of breathing that occurs upon cessation of a hypercapnic gas challenge in male mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Connexin26 mediates COCommunications biology · 2020Article
- Afferent neural feedback overrides the modulating effects of arousal, hypercapnia and hypoxaemia on neonatal cardiorespiratory control.The Journal of physiology · 2018Article
- The Critical Role of the Central Autonomic Nervous System in Fetal-Neonatal Transition.Seminars in pediatric neurology · 2018Review
- Organization of the core respiratory network: Insights from optogenetic and modeling studies.PLoS computational biology · 2018Article
- Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking.Scientific reports · 2018Article
- Theoretical perspectives on central chemosensitivity: CO2/H+-sensitive neurons in the locus coeruleus.PLoS computational biology · 2017Article
- Control of Ventilation in Health and Disease.Chest · 2017Review
- Respiratory and autonomic dysfunction in congenital central hypoventilation syndrome.Journal of neurophysiology · 2016Review
- Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis.Comprehensive Physiology · 2016Review
- Proton detection and breathing regulation by the retrotrapezoid nucleus.The Journal of physiology · 2016Review
- Neural Control of Breathing and CO2 Homeostasis.Neuron · 2015Review
- Role of the retrotrapezoid nucleus/parafacial respiratory group in coughing and swallowing in guinea pigs.Journal of neurophysiology · 2015Article
- Opioid-induced Respiratory Depression Is Only Partially Mediated by the preBötzinger Complex in Young and Adult Rabbits In Vivo.Anesthesiology · 2015Article
- Respiratory and sympathetic chemoreflex regulation by Kölliker-Fuse neurons in rats.Pflugers Archiv : European journal of physiology · 2015Article
- Impairment of Central Chemoreception in Neonatal Rats Induced by Maternal Cigarette Smoke Exposure during Pregnancy.PloS one · 2015Article
25 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
1 author at 1 institution in 1 country.
Funding
Abstract
The retrotrapezoid nucleus (RTN) contains 2,000 glutamatergic neurons that innervate selectively the respiratory centers of the pontomedullary region. These cells are at the ventral medullary surface in a previously identified chemosensitive region. RTN neurons are highly sensitive to acid in vitro and vigorously activated by inputs from the carotid body and from the hypothalamus in vivo. Mutations of the transcription factor Phox2b cause the congenital hypoventilation syndrome (CCHS), a disease characterized by extremely reduced chemoreflexes and the loss of breathing automaticity during sleep. RTN neurons express Phox2b and develop poorly in a mouse model of CCHS, which lacks chemoreflexes. Based on these and other data, I propose that the RTN is a critical nodal point for the homeostatic regulation of arterial PCO2 and that the nucleus operates as follows. RTN always contributes a major fraction of the tonic excitatory drive to the respiratory centers. RTN neurons derive their activity from two sources: a chemosensory drive (intrinsic chemosensitivity and inputs from the carotid bodies) and synaptic inputs from higher brain centers (non-chemosensory drive). Under anesthesia or non-rapid eye movement sleep, the chemosensory drive to RTN neurons dominates, and, under these circumstances, the excitatory input from RTN to the respiratory controller is required for breathing automaticity. During waking and exercise, RTN contributes a reduced fraction of the total excitatory drive to the respiratory controller, but this fraction remains essential for CO2 homeostasis because of its exquisite chemosensitivity. The working hypothesis could explain the breathing deficits experienced by CCHS patients.
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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.