Retrotrapezoid nucleus and parafacial respiratory group

The rat retrotrapezoid nucleus (RTN) contains about 2000 Phox2b-expressing glutamatergic neurons (ccRTN neurons; 800 in mice) with a well-understood developmental lineage. ccRTN neuron development fails in mice carrying a Phox2b mutation commonly present in the congenital central hypoventilation syndrome. In adulthood, ccRTN neurons regulate the breathing rate and intensity, and may regulate active expiration along with other neighboring respiratory neurons. Prenatally, ccRTN neurons form an autonomous oscillator (embryonic parafacial group, e-pF) that activates and possibly paces inspiration. The pacemaker properties of the ccRTN neurons probably vanish after birth to be replaced by synaptic drives. The neonatal parafacial respiratory group (pfRG) may represent a transitional phase during which ccRTN neurons lose their group pacemaker properties. ccRTN neurons are activated by acidification via an intrinsic mechanism or via ATP released by glia. In summary, throughout life, ccRTN neurons seem to be a critical hub for the regulation of CO2 via breathing.