Treadmill step training promotes corticospinal tract plasticity after incomplete spinal cord injury

Eisdorfer, J. T.; Nacht, H. D.; Kowalski, T.; Thackray, J. T.; Martinez, A. M.; Zymoro, L.; Phu, M. V.; Hirpara, R. R.; Danish, B. S.; Wang, R.; Khondker, A.; Eisdorfer, A. B.; Tischfield, M.; Abraira, V. E. G.

doi:10.1101/2024.10.14.618099

bioRxiv · 10.1101/2024.10.14.618099

Treadmill step training promotes corticospinal tract plasticity after incomplete spinal cord injury

Eisdorfer, J. T.·Nacht, H. D.·Kowalski, T.·Thackray, J. T.·Martinez, A. M.·Zymoro, L.·Phu, M. V.·Hirpara, R. R.·Danish, B. S.·Wang, R.·Khondker, A.·Eisdorfer, A. B.·Tischfield, M.·Abraira, V. E. G.

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Abstract

Spinal cord injury (SCI) often impairs motor functions such as voluntary movement and fine motor control, with the corticospinal tract (CST) being a crucial pathway affected. While CST-targeted rehabilitation, such as treadmill training, supports motor recovery, gaps remain in understanding the topographical changes within the CST and how they correlate with behavioral outcomes. In this study, we utilized a custom Emx1Cre;LSL-SynGFP mouse line to quantify CST plasticity following moderate contusion SCI, both with and without exercise (treadmill) training. Fluorescent labeling of cortical synapses allowed for detailed visualization of descending CST rewiring, and we assessed its relationship to behavioral outcomes, including kinematics analysis and motivational state. Mice were stratified by motivational state using the Progressive Ratio Assay, and locomotor recovery was evaluated through the Basso Mouse Scale (BMS), joint/limb kinematics, and Motion Sequencing (MoSeq) analysis. Our findings indicate that treadmill training enhances CST rewiring, especially in highly motivated animals, leading to increased synaptic density in the ventral horn and improved BMS subscores. Motivation further influenced specific kinematic parameters, such as toe clearance, while treadmill training significantly improved speed by reducing the stance phase. Results suggest that while treadmill training induces broad beneficial outcomes, motivation may fine-tune recovery, influencing neural circuit and behavioral changes. This suggests multiple mechanisms converge to promote recovery--those we cannot control and those we can. These results underscore the combined role of task-specific training and also perhaps motivation in driving CST plasticity and functional recovery after SCI.

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Eisdorfer, J. T., Nacht, H. D., Kowalski, T., Thackray, J. T., Martinez, A. M., Zymoro, L., Phu, M. V., Hirpara, R. R., Danish, B. S., Wang, R., Khondker, A., Eisdorfer, A. B., Tischfield, M., Abraira, V. E. G.. 2024-10-16. Treadmill step training promotes corticospinal tract plasticity after incomplete spinal cord injury. https://doi.org/10.1101/2024.10.14.618099

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