The neurons that restore walking after paralysis.
Details
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State: Public
Version: author
License: CC BY 4.0
UNIL restricted access
State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_6672FE6DE4F2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The neurons that restore walking after paralysis.
Journal
Nature
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
11/2022
Peer-reviewed
Oui
Volume
611
Number
7936
Pages
540-547
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord <sup>1-3</sup> applied during neurorehabilitation <sup>4,5</sup> (EES <sup>REHAB</sup> ) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EES <sup>REHAB</sup> in mice. We applied single-nucleus RNA sequencing <sup>6-9</sup> and spatial transcriptomics <sup>10,11</sup> to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type <sup>12,13</sup> and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EES <sup>REHAB</sup> , whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.
Keywords
Animals, Humans, Mice, Neurons/physiology, Paralysis/genetics, Paralysis/physiopathology, Paralysis/therapy, Spinal Cord/cytology, Spinal Cord/physiology, Spinal Cord/physiopathology, Spinal Cord Injuries/genetics, Spinal Cord Injuries/physiopathology, Spinal Cord Injuries/therapy, Walking/physiology, Electric Stimulation, Lumbosacral Region/innervation, Neurological Rehabilitation, Sequence Analysis, RNA, Gene Expression Profiling
Pubmed
Web of science
Open Access
Yes
Create date
29/11/2022 10:58
Last modification date
23/01/2024 7:16