小柯机器人

瑞士苏黎世联邦理工学院Grégoire Courtine等研究人员合作发现瘫痪后参与恢复行走的神经元。这一研究成果于2022年11月9日在线发表在国际学术期刊《自然》上。

研究人员表明，在神经康复期间对腰部脊髓进行的时空硬膜外电刺激（EES^REHAB）可恢复9名慢性脊髓损伤患者的行走。这种恢复涉及到人类在行走时腰部脊髓的神经元活动的减少。研究人员假设，这种意外的减少反映了特定神经元亚群的活动依赖性选择，而这些神经元在脊髓损伤后成为病人行走的必要条件。为了确定这些假定的神经元，研究人员在小鼠中模拟了EES^REHAB的技术和治疗特征。研究人员将单核RNA测序和空间转录组学应用于这些小鼠的脊髓，从而绘制出一个空间分辨的瘫痪恢复分子图谱。

然后，研究人员采用细胞类型和空间优先顺序来确定了参与恢复行走的神经元。分析结果中出现了一个嵌套在中间层的兴奋性中间神经元的单一群体。虽然这些神经元在脊髓损伤前不需要参与行走，但研究人员证明它们对脊髓损伤后行走的恢复与EES是必不可少的。增强这些神经元的活动能使EES^REHAB恢复行走，而去除这些神经元则能阻止中度脊髓损伤后自发的行走恢复。因此，研究人员确定了一个恢复组织的神经元亚群，它是瘫痪后恢复行走的必要和充分条件。此外，这个方法还建立了一个框架，其通过使用分子制图法来识别产生复杂行为的神经元。

据悉，脊髓损伤使大脑和脑干投射到腰部脊髓的通路中断，导致瘫痪。

附：英文原文

Title: The neurons that restore walking after paralysis

Author: Kathe, Claudia, Skinnider, Michael A., Hutson, Thomas H., Regazzi, Nicola, Gautier, Matthieu, Demesmaeker, Robin, Komi, Salif, Ceto, Steven, James, Nicholas D., Cho, Newton, Baud, Laetitia, Galan, Katia, Matson, Kaya J. E., Rowald, Andreas, Kim, Kyungjin, Wang, Ruijia, Minassian, Karen, Prior, John O., Asboth, Leonie, Barraud, Quentin, Lacour, Stphanie P., Levine, Ariel J., Wagner, Fabien, Bloch, Jocelyne, Squair, Jordan W., Courtine, Grgoire

Issue&Volume: 2022-11-09

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 cord1,2,3 applied during neurorehabilitation4,5 (EESREHAB) 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 EESREHAB in mice. We applied single-nucleus RNA sequencing6,7,8,9 and spatial transcriptomics10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type12,13 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 EESREHAB, 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.

DOI: 10.1038/s41586-022-05385-7

Source: https://www.nature.com/articles/s41586-022-05385-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html