The bulbospinal network controlling the phrenic motor system: Laterality and course of descending projections

The respiratory rhythm is generated by the parafacial respiratory group, Bötzinger complex, and pre-Bötzinger complex and relayed to pre-motor neurons, which in turn project to and control respiratory motor outputs in the brainstem and spinal cord. The phrenic nucleus is one such target, containing phrenic motoneurons (PhMNs), which supply the diaphragm, the primary inspiratory muscle in mammals. While some investigators have demonstrated both ipsi- and contralateral bulbophrenic projections, there exists controversy regarding the relative physiological contribution of each to phasic and tonic drive to PhMNs and at which levels decussations occur. Following C1- or C2 spinal cord hemisection-induced silencing of the ipsilateral phrenic/diaphragm activity, respiratory stressor-induced, as well as spontaneous, recovery of crossed phrenic activity is observed, suggesting an important contribution of pathways crossing below the level of injury in driving phrenic motor output. The precise mechanisms underlying this recovery are debated. In this review, we seek to present a comprehensive discussion of the organization of the bulbospinal network controlling PhMNs, a thorough appreciation of which is necessary for understanding neural respiratory control, accurate interpretation of studies investigating respiratory recovery following spinal cord injury, and targeted development of therapies for respiratory neurorehabilitation in patients sustaining high cervical cord injury.