Neurogenic mechanisms for locomotor-respiratory coordination in mammals

Abstract

Central motor rhythm-generating networks controlling different functions are generally considered to operate mostly independently from one another, each controlling the specific behavioral task to which it is assigned. However, under certain physiological circumstances, central pattern generators (CPGs) can exhibit strong uni- or bidirectional interactions that render them closely inter-dependent. One of the best illustrations of such an inter-CPG interaction is the functional relationship that may occur between rhythmic locomotor and respiratory functions. It is well known that in vertebrates, lung ventilatory rates accelerate at the onset of physical exercise in order to satisfy the accompanying rapid increase in metabolism. Part of this acceleration is sustained by a coupling between locomotion and ventilation, which most often results in a periodic drive of the respiratory cycle by the locomotor rhythm. In terrestrial vertebrates, the likely physiological significance of this coordination is that it serves to reduce the mechanical interference between the two motor systems, thereby producing an energetic benefit and ultimately, enabling sustained aerobic activity. Several decades of studies have shown that locomotor-respiratory coupling is present in most species, independent of the mode of locomotion employed. The present article aims to review and discuss mechanisms engaged in shaping locomotor-respiratory coupling (LRC), with an emphasis on the role of sensory feedback inputs, the direct influences between CPG networks themselves, and finally on spinal cellular candidates that are potentially involved in the coupling of these two vital motor functions.

Keywords: breathing rate modulation; limb proprioceptive inputs; locomotor-respiratory coupling; lumbar glutamatergic neurons; neural network interactions.

Figure 1

Locomotor-respiratory coupling (LRC) ratios in the animal kingdom. (A–C), Graphical representation of the most common LRC ratios observed in mammals (A), and birds (B,C). The colored dots indicate the LRC ratios commonly observed, depending on the mode of locomotion used, in mammals (red, gallop; blue, trot; green, hopping/bond; purple, bipedal running), and birds (green, running; orange, flying). Note that for the same gait either one (e.g. gallop) or several (e.g., trot) LRC can be observed. Adapted from Boggs (2002); Stickford and Stickford (2014).

Figure 2

Summary schematics of the neurogenic pathways contributing to locomotor-respiratory coupling (A) and locomotion-derived breathing rate modulation (B). 1, Ascending projections from limb sensory afferents to the PB/KF complex; 2, Pathway enabling spinal proprioceptive afferents to modulate the excitability of spinal inspiratory motoneurons via a GABA-releasing relay; 3, Parallel descending drives from the MLR to the spinal locomotor CPG and to the PBC; 4, Efference copy signals conveyed by ascending glutamatergic projections from the spinal locomotor CPG to respiratory CPG networks through an SP-releasing relay; 5, Propriospinal pathway enabling the locomotor CPG to modulate activity of spinal expiratory neurons. Abd., abdominal muscles; CPG, central pattern generator; Diaph., diaphragm; exp., expiratory neurons; insp., inspiratory neurons; MLR, mesencephalic locomotor region; Mn, motoneurons; PBC, preBötzinger Complex; PB/KF, parabrachial/Kölliker-Fuse nucleus; pFRG, parafacial respiratory group; RF, reticular formation; SP, substance P. Adapted from Morin and Viala (2002); Giraudin et al. (2008, 2012); Le Gal et al. (2016, 2020).