Restorative and Compensatory Respiratory Plasticity Following Cervical Spinal Cord Injury (SCI)

Abstract

Spontaneous recovery of diaphragm function ipsilateral to a complete lateral C2 hemisection (C2Hx) is an established example of “restorative respiratory plasticity”. The extent of recovered ipsilateral phrenic motoneuron activity is limited, however, and its impact on breathing has not been extensively investigated. The present study was conducted to test the hypothesis that contralateral “compensatory plasticity” plays a much greater role and is accompanied by connectivity changes associated with the contralateral phrenic circuitry.Using combined anterograde and transneuronal retrograde tracing (with biotin dextran amine (BDA) and pseudorabies virus (PRV), respectively), we recently demonstrated that cells within the medulla innervate the phrenic motoneurons (PhMNs) both directly and indirectly (via interneurons; INs). More recent experiments have revealed reduced bulbospinal inputs to PhMNs ipsilateral to injury, as well as to associated pre‐phrenic INs. PRV tracing phrenic pathways ipsilateral to injury also showed decreased IN‐PhMN connectivity. In contrast, PRV tracing of phrenic pathways contralateral to injury demonstrate some bilateral recruitment of INs at C1 which are not infected under similar labeling conditions in normal rats. These results indicate neural substrate changes that may underlie restorative versus compensatory ventilatory behavior after high cervical SCI.Grant Funding Source: NIH; Craig H. Neilsen Foundation; Anne & Oscar Lackner Chair in Neuroscience