Breathing matters

Abstract

Breathing is a well-described, vital and surprisingly complex behaviour, with behavioural and physiological outputs that are easy to directly measure. Key neural elements for generating breathing pattern are distinct, compact and form a network amenable to detailed interrogation, promising the imminent discovery of molecular, cellular, synaptic and network mechanisms that give rise to the behaviour. Coupled oscillatory microcircuits make up the rhythmic core of the breathing network. Primary among these is the preBötzinger Complex (preBötC), which is composed of excitatory rhythmogenic interneurons and excitatory and inhibitory pattern-forming interneurons that together produce the essential periodic drive for inspiration. The preBötC coordinates all phases of the breathing cycle, coordinates breathing with orofacial behaviours and strongly influences, and is influenced by, emotion and cognition. Here, we review progress towards cracking the inner workings of this vital core.

Development of the brainstem respiratory circuit

“…It is hard to pinpoint the neural correlates of the perinatal changes in respiratory control because the respiratory circuit consists of over a dozen functionally diverse respiratory nuclei that are anatomically scattered throughout the brainstem. Hereafter follows a brief summary of the components of the respiratory circuit and their function, but see Del Negro et al, and Ramirez & Baertsch, for two excellent recent reviews on the function of the respiratory circuit. Some respiratory nuclei have intrinsic rhythmic properties and generate the respiratory rhythms.…”

“…These neurons either send their signals onto premotor neurons or act as premotor neurons themselves, resulting in the characteristic rhythmic breathing movements. In turn, rhythmic nuclei receive input from higher order neurons and chemosensitive cells to enable coordination with orofacial movements and to maintain respiratory homeostasis, respectively (Figure ) (Alheid, Milsom, & McCrimmon, ; Del Negro et al, ; J. C. Smith et al, ). Thus, in the respiratory circuitry, continuity and versatility go hand in hand to enable all aspects of respiratory control.…”

“…There are three respiratory nuclei with intrinsic rhythmogenic properties, each of which fires during a distinct phase of the respiratory cycle: inspiration, post‐inspiration, and expiration (Ramirez & Baertsch, ). The preBötzinger complex (preBötC), which is both necessary and sufficient for the generation of inspiratory rhythms in adult mice, is active during all breaths and forms the stable core of the respiratory pattern generator (Alheid & McCrimmon, ; Dubreuil, Barhanin, et al, ; Guyenet & Bayliss, ; Del Negro et al, ; Ramirez & Baertsch, ; J. C. Smith et al, ; Smith et al, ). The activity of the other two rhythmic nuclei, however, get recruited on a breath‐to‐breath basis.…”

“…The postinspiratory complex (PiCo) is active during the postinspiratory phase. This phase contributes to respiration by increasing the time air remains in the lungs and prolonging the period of gas exchange, and by promoting laminar expiratory airflow to minimize airway resistance and diminish the likelihood for airway collapse (Del Negro et al, ). Additionally, the postinspiratory phase is associated with nonrespiratory behaviors including vocalization and swallowing.…”

“…Additionally, breathing rhythms must be coordinated with orofacial behaviors such as vocalization and swallowing, which are important for social interaction and to prevent congestion of the airways during feeding. Thus, even though breathing seems simple, the circuit that controls it is remarkably complex (Alheid & McCrimmon, ; Dubreuil, Barhanin, Goridis, & Brunet, ; Guyenet & Bayliss, ; Del Negro, Funk, & Feldman, ; Ramirez & Baertsch, ; J. C. Smith, Abdala, Borgmann, Rybak, & Paton, ).…”