The conditional nature of the “Central Rhythm Generator” and the production of episodic breathing

Episodic breathing patterns have been observed in species of all vertebrate classes under certain conditions and/or at certain times in development. This breathing pattern can be considered part of a continuum between no breathing and continuous breathing. In birds and mammals it is also generally part of a developmental continuum in which episodic breathing occurs early in development and rarely in adults. Production of this pattern appears to be an intrinsic property of the medullary rhythm generating mechanism (possibly due to interactions between different rhythm generating sites) that is stabilized by pontine or midbrain inputs and, in intact animals, is primarily regulated by afferent inputs from chemoreceptors and pulmonary stretch receptors; i.e. there is a hierarchy of control. In all cases, episodes appear to be produced by quantal expression of a fundamental rhythm. At present NO, GABAA and glycine mediated processes, and possibly μ-opioid receptor mediated processes, are implicated in the clustering of breaths into episodes. The inter-breath interval, which may occur at either the end of the inspiratory or the expiratory phase in different species, is the primary regulated variable in this pattern. The biological significance of clustering breaths into episodes may relate to reducing the oxidative cost of breathing, enhancing gas exchange or minimizing oxidative damage to tissues.