ArticleThe Journal of physiology2008
Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apnoeic threshold in rats.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 159 citations in OpenAlex.
- Redefining PHOX2B-Related Neurodevelopmental Disorders as Circuitopathies: A New Paradigm in Autonomic Network Medicine.Neuroscience bulletin · 2026Review
- GABAergic Inhibition from the Nucleus Tractus Solitarius to Ventrolateral Medulla Phox2b Neurons Modulates Central Respiratory Chemoreflex and Ventilatory Homeostasis.Neuroscience bulletin · 2026Article
- Sex Differences in the Effects of Etonogestrel on Respiratory Recovery in an In Vivo Rat Model of Central Chemoreflex Impairment.Acta physiologica (Oxford, England) · 2026Article
- Tachykinergic signaling mediated by NK1 receptors in the respiratory parafacial region drives respiratory output and contributes to the chemoreflex response to COPflugers Archiv : European journal of physiology · 2026Article
- Functional modulation of retrotrapezoid neurons drives fentanyl-induced respiratory depression.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Characterisation of putative retrotrapezoid nucleus (RTN) chemoreceptor neurons in the adult human brainstem.Brain structure & function · 2025Article
- Afferent and Efferent Connections of the Postinspiratory Complex (PiCo) Revealed by AAV and Monosynaptic Rabies Viral Tracing.The Journal of comparative neurology · 2024Article
- Article
- Loss-of-function of chemoreceptor neurons in the retrotrapezoid nucleus: What have we learned from it?Respiratory physiology & neurobiology · 2024Article
- Revisiting the Role of Serotonin in Sleep-Disordered Breathing.International journal of molecular sciences · 2024Review
- Neuromedin B-Expressing Neurons in the Retrotrapezoid Nucleus Regulate Respiratory Homeostasis and Promote Stable Breathing in Adult Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Review
- Potential Role of the Retrotrapezoid Nucleus in Mediating Cardio-Respiratory Dysfunction in Heart Failure With Preserved Ejection Fraction.Frontiers in physiology · 2022Review
- The retrotrapezoid nucleus and the neuromodulation of breathing.Journal of neurophysiology · 2021Review
- KGlia · 2021Article
- Respiratory Control by Phox2b-expressing Neurons in a Locus Coeruleus-preBötzinger Complex Circuit.Neuroscience bulletin · 2021Article
- Multi-Level Regulation of Opioid-Induced Respiratory Depression.Physiology (Bethesda, Md.) · 2020Review
- Stimulation of retrotrapezoid nucleus Phox2b-expressing neurons rescues breathing dysfunction in an experimental Parkinson's disease rat model.Brain pathology (Zurich, Switzerland) · 2020Article
- Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure.American journal of physiology. Lung cellular and molecular physiology · 2020Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Injection of the neurotoxin saporin-substance P (SSP-SAP) into the retrotrapezoid nucleus (RTN) attenuates the central chemoreflex in rats. Here we ask whether these deficits are caused by the destruction of a specific type of interneuron that expresses the transcription factor Phox2b and is non-catecholaminergic (Phox2b(+)TH(-)). We show that RTN contains around 2100 Phox2b(+)TH(-) cells. Injections of SSP-SAP into RTN destroyed Phox2b(+)TH(-) neurons but spared facial motoneurons, catecholaminergic and serotonergic neurons and the ventral respiratory column caudal to the facial motor nucleus. Two weeks after SSP-SAP, the apnoeic threshold measured under anaesthesia was unchanged when fewer than 57% of the Phox2b(+)TH(-) neurons were destroyed. However, destruction of 70 +/- 3.5% of these cells was associated with a dramatic rise of the apnoeic threshold (from 5.6 to 7.9% end-expiratory P(CO(2))). In anaesthetized rats with unilateral lesions of around 70% of the Phox2b(+)TH(-) neurons, acute inhibition of the contralateral intact RTN with muscimol instantly eliminated phrenic nerve discharge (PND) but normal PND could usually be elicited by strong peripheral chemoreceptor stimulation (8/12 rats). Muscimol had no effect in rats with an intact contralateral RTN. In conclusion, the destruction of the Phox2b(+)TH(-) neurons is a plausible cause of the respiratory deficits caused by injection of SSP-SAP into RTN. Two weeks after toxin injection, 70% of these cells must be killed to cause a severe attenuation of the central chemoreflex under anaesthesia. The loss of an even greater percentage of these cells would presumably be required to produce significant breathing deficits in the awake 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.