Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity

Abstract

SUMMARYBreathing automaticity and CO 2 regulation are inseparable neural processes. The retrotrapezoid nucleus (RTN), a group of glutamatergic neurons that express the transcription factor Phox2b, may be a crucial nodal point through which breathing automaticity is regulated to maintain CO 2 constant. This review updates the analysis presented in prior publications. Additional evidence that RTN neurons have central respiratory chemoreceptor properties is presented but this is only one of many factors that determine their activity. The RTN is also regulated by powerful inputs from the carotid bodies and, at least in the adult, by many other synaptic inputs. We also analyze how RTN neurons may control the activity of the downstream central respiratory pattern generator. Specifically, we review the evidence which suggests that RTN neurons a) innervate the entire ventral respiratory column, and b) control both inspiration and expiration. Finally, we argue that the RTN neurons are the adult form of the parafacial respiratory group in neonate rats.

Breathing without CO2Chemosensitivity in ConditionalPhox2bMutants

“…This difference was greatly enhanced when the calculation of mean ventilation included apnea periods. RRG requires excitatory inputs, among which that afforded by CO 2 has been considered as crucial (Phillipson et al, 1981;Takakura et al, 2008;Guyenet et al, 2009;Spyer and Gourine, 2009). In previous work, we have produced mice with different mutations in Phox2b-either the toxic Phox2b 27Ala mutation that causes CCHS in man or conditional null mutations-both of which compromise RTN neuron differentiation (Dubreuil et al, 2008).…”

Fatal breathing dysfunction in a mouse model of Leigh syndrome

“…In some cases, microglial activation extended to their projections, accompanied by mild microgliosis in the preBötC that was identified by neurokinin 1 receptor immunolabeling (Supplemental Figure 2, A-D), suggesting that the alterations in these neurons was not sufficient to elicit a severe secondary inflammatory response. No degenerative changes were detected in the chemoreceptive Phox2B-immunoreactive neurons of the retrotrapezoid nucleus (31,32). Selective inactivation of Ndusf4 in the VN induces neurodegeneration and breathing abnormalities and increases mortality.…”

Calcium imaging of neuronal activity in the most rostral parafacial respiratory group of the newborn rat

“…The rostral pFRG is thought to contain CO 2 -sensitive neurons and overlaps at least partly with the retrotrapezoid nucleus (RTN), which is considered to play a role in central chemoreception [15][16][17]. Therefore, we tested the change in fluorescence in this region following hypercapnic stimulation in the presence of TTX.…”