Maturation of the Mammalian Respiratory System

Abstract

In this review, the maturational changes occurring in the mammalian respiratory network from fetal to adult ages are analyzed. Most of the data presented were obtained on rodents using in vitro approaches. In gestational day 18 (E18) fetuses, this network functions but is not yet able to sustain a stable respiratory activity, and most of the neonatal modulatory processes are not yet efficient. Respiratory motoneurons undergo relatively little cell death, and even if not yet fully mature at E18, they are capable of firing sustained bursts of potentials. Endogenous serotonin exerts a potent facilitation on the network and appears to be necessary for the respiratory rhythm to be expressed. In E20 fetuses and neonates, the respiratory activity has become quite stable. Inhibitory processes are not yet necessary for respiratory rhythmogenesis, and the rostral ventrolateral medulla (RVLM) contains inspiratory bursting pacemaker neurons that seem to constitute the kernel of the network. The activity of the network depends on CO2 and pH levels, via cholinergic relays, as well as being modulated at both the RVLM and motoneuronal levels by endogenous serotonin, substance P, and catecholamine mechanisms. In adults, the inhibitory processes become more important, but the RVLM is still a crucial area. The neonatal modulatory processes are likely to continue during adulthood, but they are difficult to investigate in vivo. In conclusion, 1) serotonin, which greatly facilitates the activity of the respiratory network at all developmental ages, may at least partly define its maturation; 2) the RVLM bursting pacemaker neurons may be the kernel of the network from E20 to adulthood, but their existence and their role in vivo need to be further confirmed in both neonatal and adult mammals.

Optical recording from respiratory pattern generator of fetal mouse brainstem reveals a distributed network

“…Changes that occur in respiratory mechanisms as the foetus develops and becomes adult have been studied in several mammals (Hilaire and Duron, 1999), with emphasis on regulatory mechanisms, and the possible role of pacemaker neurons at successive stages (Del Negro et al, 2005;Peña et al, 2004). Maps of respiratory activity in newborn rat and mouse made with voltage sensitive dyes suggested that the respiratory activity started in each cycle on a discrete group of neurons located in the para-facial region, and then it was propagated caudally into the pre-Bötzinger complex level (Onimaru and Homma, 2003;Onimaru et al, 2004).…”

Diversity of Functional Astroglial Properties in the Respiratory Network

“…In this context, it is noteworthy that we did not detect TUC-4 labeling in the ventral respiratory group of the early postnatal brainstem (P2), indicating that neuronal network formation and principal wiring have been completed at birth. Reorganization and adaptation of the synaptic architecture, however, have to be tailored to functional requirements during postnatal development (for review, see Hilaire and Duron, 1999;Richter and Spyer, 2001). Especially during the first 2 postnatal weeks, there are ongoing changes in the density of glutamate receptors on respiratory neurons (Liu and Wong-Riley, 2002).…”

Altered Respiratory Activity and Respiratory Regulations in Adult Monoamine Oxidase A-Deficient Mice

“…The nervous control of respiration that has been studied in vivo for several decades, mainly in adult cats, is now being studied in vitro in the neonatal rodent (Hilaire and Duron, 1999) because its respiratory network remains functional in vitro. There is little information regarding the in vivo respiration of the adult mouse (Tankersley et al, 1997(Tankersley et al, , 1999.…”