The parafacial respiratory group and the control of active expiration

Breathing at rest is typically characterized by three phases: active inspiration, post-inspiration (or stage 1 expiration), and passive expiration (or stage 2 expiration). Breathing during periods of increased respiratory demand, on the other hand, engages active expiration through recruitment of abdominal muscles in order to increase ventilation. It is currently hypothesized that different phases of the respiratory rhythm are driven by three coupled oscillators: the preBötzinger Complex, driving inspiration, the parafacial respiratory group (pFRG), driving active expiration and the post-inspiratory Complex, driving post-inspiration. In this paper we review advances in the understanding of the pFRG and its role in the generation of active expiration across different developmental stages and vigilance states. Recent experiments suggest that the abdominal recruitment varies across development depending on the vigilance state, possibly following the maturation of the network responsible for the generation of active expiration and neuromodulatory systems that influence its activity. The activity of the pFRG is tonically inhibited by GABAergic inputs and strongly recruited by cholinergic systems. However, the sources of these modulatory inputs and the physiological conditions under which these mechanisms are used to recruit active expiration and increase ventilation need further investigation. Some evidence suggests that active expiration during hypercapnia is evoked through disinhibition, while during hypoxia it is elicited through activation of catecholaminergic C1 neurons. Finally, a discussion of experiments indicating that the pFRG is anatomically and functionally distinct from the adjacent and partially overlapping chemosensitive neurons of the retrotrapezoid nucleus is also presented.