The Retrotrapezoid Nucleus and Breathing
The retrotrapezoid nucleus (RTN) is located in the rostral medulla oblongata close to the ventral surface and consists of a bilateral cluster of glutamatergic neurons that are non-aminergic and express homeodomain transcription factor Phox2b throughout life. These neurons respond vigorously to increases in local pCO2 via cell-autonomous and paracrine (glial) mechanisms and receive additional chemosensory information from the carotid bodies. RTN neurons exclusively innervate the regions of the brainstem that contain the respiratory pattern generator (RPG). Lesion or inhibition of RTN neurons largely attenuates the respiratory chemoreflex of adult rats whereas their activation increases respiratory rate, inspiratory amplitude and active expiration. Phox2b mutations that cause congenital central hypoventilation syndrome in humans prevent the development of RTN neurons in mice. Selective deletion of the RTN Phox2b-VGLUT2 neurons by genetic means in mice eliminates the respiratory chemoreflex in neonates.
In short, RTN Phox2b-VGLUT2 neurons are a major nodal point of the CNS network that regulates pCO2 via breathing and these cells are probable central chemoreceptors.
KeywordsBreathing network Chemoreflexes Central chemoreceptors Retrotrapezoid nucleus Congenital central hypoventilation syndrome Phox2b Optogenetics
- Bochorishvili G, Stornetta RL, Coates MB, Guyenet PG (2011) Pre-Bötzinger complex receives glutamatergic innervation from galaninergic and other retrotrapezoid nucleus neurons. J Comp Neurol 520(5):1047–1061Google Scholar