The neurons that restore walking after paralysis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA764235 | ENA |
REPOSITORIES: ENA
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Project description:The neurons that restore walking after paralysis [spatial transcriptomics]
| PRJNA764238 | ENA
Project description:The neurons that restore walking after paralysis [snRNA-seq]
| PRJNA764239 | ENA
Project description:Here, we show that epidural electrical stimulation (EES) of the lumbar spinal cord applied during neurorehabilitation (EESREHAB) restored walking in nine people with chronic spinal cord injury (SCI). This recovery involved 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. To identify these putative neurons, we modelled 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 chart a spatially-resolved molecular atlas of recovery from paralysis. We then employed cell type and spatial prioritization to uncover the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons were not necessary to walk before SCI, we demonstrate that they are essential to regain walking following SCI. In turn, augmenting their activity instantly phenocopied the recovery of walking enabled by EESREHAB. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after SCI. Moreover, our methodology establishes a framework to identify the neurons producing complex behaviours using molecular cartography.
2022-06-20 | GSE184369 | GEO
Project description:Here, we show that epidural electrical stimulation (EES) of the lumbar spinal cord applied during neurorehabilitation (EESREHAB) restored walking in nine people with chronic spinal cord injury (SCI). This recovery involved 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. To identify these putative neurons, we modelled 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 chart a spatially-resolved molecular atlas of recovery from paralysis. We then employed cell type and spatial prioritization to uncover the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons were not necessary to walk before SCI, we demonstrate that they are essential to regain walking following SCI. In turn, augmenting their activity instantly phenocopied the recovery of walking enabled by EESREHAB. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after SCI. Moreover, our methodology establishes a framework to identify the neurons producing complex behaviours using molecular cartography.
2022-06-20 | GSE184370 | GEO
Project description:Although axon regeneration can now be induced experimentally across anatomically complete spinal cord injury (SCI), restoring meaningful function after such injuries has been elusive. This failure contrasts with the spontaneous, naturally occuring repair that restores walking after severe but incomplete SCI. Here, we applied projection-specific and comparative single-nucleus RNA sequencing to uncover the transcriptional phenotype and connectome of neuronal subpopulations involved in natural spinal cord repair. We identified a molecularly defined population of excitatory projection neurons in the thoracic spinal cord that extend axons to the lumbar spinal cord where walking execution centers reside. We show that regrowing axons from these specific neurons across anatomically complete SCI and guiding them to reconnect with their appropriate target region in the lumbar spinal cord restores walking in mice. These results demonstrate that mechanism-based repair strategies that recapitulate the natural topology of molecularly defined neuronal subpopulations can restore neurological functions. Expanding this principle to different classes of neurons across the central nervous system may unlock the framework to achieve complete repair of the injured spinal cord.
2023-09-20 | GSE198949 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-20 | GSE184371 | GEO
Project description:Cricket paralysis virus Transcriptome or Gene expression
| PRJNA248688 | ENA
Project description:Patients with Alzheimer’s disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether modulating AHN is sufficient to improve these cognitive and noncognitive symptoms in AD remains elusive. Here we report that chronic stimulation of hypothalamic supramammillary nucleus (SuM) during early AD restores AHN in an otherwise impaired neurogenic niche. Strikingly, activation of SuM-enhanced adult-born neurons (ABNs) is sufficient to restore memory and emotion deficits in 5×FAD mice. Interestingly, activation of SuM-enhanced ABNs in AD mice increases CA3 and CA1 activity. To probe ABN-activity-dependent changes, we performed quantitative phosphoproteomics and found activation of SuM-enhanced ABNs promotes activation of the canonical pathways related to synaptic plasticity and microglia phagocytosis. Functional assays further confirm increased CA1 long-term potentiation and enhanced microglia phagocytosis of plaques upon activation of SuM-enhanced ABNs. Our findings reveal a robust AHN-promoting strategy that is sufficient to restore AD-associated deficits and highlight ABN-activity-dependent mechanisms underlying functional improvement in AD.
2023-03-08 | PXD034176 | Pride
Project description:The functional state of denervated muscle is a critical factor in the ability to restore movement after injury- or disease-related paralysis. Here we used peripheral optogenetic stimulation in the mouse whisker system to investigate the time course of changes in nerve and muscle function following facial nerve transection. While most skeletal muscles atrophy after lower motor neuron denervation, optogenetic muscle stimulation of the paralyzed whisker pad revealed sustained increases in the sensitivity, velocity, and amplitude of whisker movements, and reduced fatigability, starting 48 h after denervation. Transcriptome profiling showed distinct regulation of multiple gene families in denervated whisker pad muscles compared to the atrophy-prone soleus, including prominent changes in ion channels and contractile fibers. Together, our results define the functional and transcriptomic landscape of muscle denervation supersensensitivty, and have implications for restoring movement after neuromuscular injury or disease.
2018-11-19 | GSE121590 | GEO
Project description:We present a machine-learning method to prioritize the cell types most responsive to biological perturbations within high-dimensional single-cell data. We validate our method, Augur (https://github.com/neurorestore/Augur), on a compendium of single-cell RNA-seq, chromatin accessibility, and imaging transcriptomics datasets. We apply Augur to expose the neural circuits that enable walking after paralysis in response to spinal cord neurostimulation.
2020-06-05 | GSE142245 | GEO