Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat

Abstract

Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. In uninjured animals, conditionally silencing LAPNs resulted in disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping in the adult rat. Given their ventrolateral location in the spinal cord white matter, many LAPN axons likely remain intact following thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would result in diminished hindlimb locomotor function. We found instead that silencing of spared LAPNs post-SCI restored the left-right hindlimb coordination associated with alternating gaits that was lost as a result of SCI. Several other fundamental characteristics of hindlimb stepping were also improved and the number of abnormal steps were reduced. However, hindlimb-forelimb coordination was not restored. These data suggest that the temporal information carried between the enlargements by the LAPNs after SCI may be detrimental to hindlimb locomotor function. These observations have implications for our understanding of the relationship between injury severity and functional outcome, for the efforts to develop neuro- and axo-protective therapeutic strategies, and also for the clinical study/implementation of spinal stimulation and neuromodulation.