Abstract: : Rehabilitation enabled by epidural electrical stimulation of the lumbar spinal cord (EESREHAB) after chronic spinal cord injury (SCI) leads to robust functional improvement and restores walking. This recovery is associated with a reduction of the metabolic activity in the lumbar spinal cord during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential to walk after SCI. After modelling all the technological and therapeutic features underlying EESREHAB in mice, we applied single-nucleus RNA sequencing and spatial transcriptomics to the spinal cord of these mice to uncover the neurons involved in the recovery of walking. A single population of excitatory interneurons located in intermediate laminae emerged. Although these neurons were not necessary to walk before SCI, we demonstrate that they are essential to regain walking following SCI using chemogenetic and optogenetic silencing. In turn, augmenting their activity instantly phenocopied the recovery of walking enabled by EESREHAB. Thus, we identified a neuronal subpopulation that is necessary and sufficient to regain walking after paralysis.
Organizer
Sadaf Soloukey
s.soloukeytbalvandany@erasmusmc.nl