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The ventral surface of the rostral medulla oblongata has been suspected since the 1960s to harbor central respiratory chemoreceptors [i.e., acid-activated neurons that regulate breathing to maintain a constant arterial PCO (PaCO)]. The key neurons, a.k.a. the retrotrapezoid nucleus (RTN), have now been identified. In this review we describe their transcriptome, developmental lineage, and anatomical projections. We also review their contribution to CO homeostasis and to the regulation of breathing automaticity during sleep and wake. Finally, we discuss several mechanisms that contribute to the activation of RTN neurons by COin vivo: cell-autonomous effects of protons; paracrine effects of pH mediated by surrounding astrocytes and blood vessels; and excitatory inputs from other CO-responsive CNS neurons.
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http://dx.doi.org/10.1016/j.tins.2019.09.002 | DOI Listing |
J Physiol
September 2025
Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, São Paulo, Brazil.
The retrotrapezoid nucleus, located in the parafacial medullary region (RTN/pFRG), is crucial for respiratory activity and central chemoreception. Recent evidence suggests that neuromodulation, including peptidergic signalling, can influence the CO/H sensitivity of RTN neurons. The paraventricular nucleus of the hypothalamus (PVN) projects to the ventral medullary surface, including the RTN, and is considered the primary source of oxytocin to the brainstem.
View Article and Find Full Text PDFTrends Neurosci
August 2025
Genomics and Computational Biology, PhD Program, Virginia Tech, Blacksburg, VA, USA; School of Neuroscience, Virginia Tech, Blacksburg, VA, USA.
The brain regulates breathing in response to changes in CO/H by a process referred to as respiratory chemoreception. The retrotrapezoid nucleus (RTN) is essential for this function. RTN neurons are intrinsically activated by CO/H.
View Article and Find Full Text PDFBrain Struct Funct
August 2025
Faculty of Medicine and Health, The University of New South Wales, Sydney, NSW, 2052, Australia.
The retrotrapezoid nucleus (RTN) of rodents is located ventral to the facial motor nucleus (7N) and consists of acid-sensitive neurons that activate breathing and mediate the central component of the ventilatory response to hypercapnia. In rodents, RTN neurons can be histologically identified by the presence of paired-like homeobox 2B positive nuclei (Phox2b +) and the absence of cytoplasmic choline acetyltransferase (ChAT-) and tyrosine hydroxylase (TH-). Up to 50% of rodent RTN neurons synthesise galanin, and 88% express pituitary adenylate cyclase activating polypeptide (PACAP).
View Article and Find Full Text PDFNeuron
July 2025
Department of Applied Science, School of Computing, Data Sciences & Physics, William & Mary, Williamsburg, VA 23185, USA. Electronic address:
Breathing movements depend on rhythmic neural activity in brainstem nuclei whose constituent neurons are well characterized. Knowing the sites and cells underlying the behavior enables us to identify the roles of individual ion channels. They accomplish three tasks: regulate excitability via the balance of intrinsic currents that govern baseline membrane potential and tonic firing; generate bursts to drive the motor output pattern; and transduce blood-gas levels, lung volume, and air qualities.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
September 2025
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, United States.
The primary cause of death from opioid overdose is opioid-induced respiratory depression (OIRD), characterized by severe suppression of respiratory rate, destabilized breathing patterns, hypercapnia, and heightened risk of apnea. The retrotrapezoid nucleus (RTN), a critical chemosensitive brainstem region in the rostral ventrolateral medullary reticular formation, contains Phox2b/neuromedin-B () propriobulbar neurons. These neurons, stimulated by CO/H, regulate breathing to prevent respiratory acidosis.
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