Retrotrapezoid nucleus and parafacial respiratory group

Abstract

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.

Central Neurogenic Hyperventilation in Anti-NMDA Receptor Encephalitis

“…The hyperglutamatergic state, together with a decrease in the pH of the CSF, might lead to depression of the central chemoreceptor activity provided by the arcuate nucleus, the human analogue of the chemically-coded retrotrapezoid nucleus (ccRTN), in patients with NMDA receptor encephalitis (5,9). The depression of the ccRTN results not only in a reduced respiratory response to central and peripheral chemoreceptors, but also in severe hypoventilation, especially during sleep.…”

Neural mechanisms underlying respiratory rhythm generation in the lamprey

“…the hypothesized rostral expiratory oscillator of mammals (see e.g. Onimaru et al, 2009;Thoby-Brisson et al, 2009;Guyenet and Mulkey, 2010;Feldman et al, 2013;Smith et al, 2013). This oscillator may display burst activity involving endogenous I NaP -dependent properties, as it occurs in the preBötC ThobyBrisson et al, 2009;Molkov et al, 2010).…”

“…This oscillator may display burst activity involving endogenous I NaP -dependent properties, as it occurs in the preBötC ThobyBrisson et al, 2009;Molkov et al, 2010). In addition, it contains glutamatergic neurons that express NK1 receptors, but it is not sensitive to opioids (Mulkey et al, 2004;Onimaru et al, 2008;Takakura et al, 2008;Lazarenko et al, 2009;Thoby-Brisson et al, 2009; for reviews, see Feldman et al, 2013;Guyenet and Mulkey, 2010). In conclusion, similarly to other neurophysiological features (Ericsson et al, , 2013Stephenson-Jones et al, 2011, 2012a, 2012b, the basic oscillatory and neuromodulatory mechanisms of the respiratory network seem to be highly evolutionary conserved regardless of their location and their inspiratory or expiratory function.…”

Sources of Inspiration: A Neurophysiologic Framework for Understanding Anesthetic Effects on Ventilatory Control

“…In ''en bloc'' preparations (in which the brainstem through the thorax is harvested from the animal with neurologic connections remaining intact), the innate electrical activity of preBOTc and RTN/pFRG neurons closely precedes depolarization of the phrenic nerves, suggesting that either of these sites might be the true ventilatory pacemaker. In keeping with these observations, the preBOTc was often referred to in the literature as the putative pacemaker, while the RTN/ pFRG neurons were designated ''pre-inspiratory'' (pre-I) neurons [19]. However, as Guyenet and Mulkey [19] observe, the pre-I nomenclature fails to account for the fact that RTN/pFRG neurons generate action potentials both before and after depolarization of the phrenic nerve; in fact, the majority of RTN/pFRG activity occurs after the phrenic nerve discharges.…”