C. Kathe†, M. Skinnider†, T. Hutson†, N. Regazzi, M. Gautier, R. Demesmaeker, S. Komi,S. Ceto, N. James, N. Cho, L. Baud, K. Galan, K. Matson, A. Rowald, K. Kim, R. Wang,J. Prior, L. Asboth, Q. Barraud, S. Lacour, A. Levine, F. Wagner, J. Bloch†, J. Squair†, and G. Courtine†
Abstract
A spinal cord injury interrupts pathways from the brain and brainstem that project tothe lumbar spinal cord, leading to paralysis. Here we show that spatiotemporalepidural electrical stimulation (EES) of the lumbar spinal cord1–3 applied duringneurorehabilitation4,5 (EESREHAB) restored walking in nine individuals with chronicspinal cord injury. This recovery involved a reduction in neuronal activity in thelumbar spinal cord of humans during walking. We hypothesized that this unexpectedreduction reflects activity-dependent selection of specific neuronal subpopulationsthat become essential for a patient to walk after spinal cord injury. To identify theseputative neurons, we modelled the technological and therapeutic featuresunderlying EESREHAB in mice. We applied single-nucleus RNA sequencing6–9 and spatialtranscriptomics10,11 to the spinal cords of these mice to chart a spatially resolvedmolecular atlas of recovery from paralysis. We then employed cell type12,13 and spatialprioritization to identify the neurons involved in the recovery of walking. A singlepopulation of excitatory interneurons nested within intermediate laminae emerged.Although these neurons are not required for walking before spinal cord injury, wedemonstrate that they are essential for the recovery of walking with EES followingspinal cord injury. Augmenting the activity of these neurons phenocopiedthe recovery of walking enabled by EESREHAB, whereas ablating them prevented therecovery of walking that occurs spontaneously after moderate spinal cord injury.We thus identified a recovery-organizing neuronal subpopulation that is necessaryand sufficient to regain walking after paralysis. Moreover, our methodologyestablishes a framework for using molecular cartography to identify the neuronsthat produce complex behaviours.
Scientists in Switzerland identified the neuron in the spinal cord that restores walking after spinal cord injury. .NeuroRestore