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The neurons that restore walking after paralysis [spatial transcriptomics]

ABSTRACT: The neurons that restore walking after paralysis [spatial transcriptomics]

PROVIDER: PRJNA764238 | ENA |

REPOSITORIES: ENA

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The neurons that restore walking after paralysis [spatial transcriptomics]

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

The neurons that restore walking after paralysis

Project description:The neurons that restore walking after paralysis

| PRJNA764235 | ENA

The neurons that restore walking after paralysis [snRNA-seq]

Project description:The neurons that restore walking after paralysis [snRNA-seq]

| PRJNA764239 | ENA

The neurons that restore walking after paralysis [snRNA-seq]

2022-06-20 | GSE184370 | GEO

Spinal cord regeneration at single-cell resolution restores walking after paralysis

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

The neurons that restore walking after paralysis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-20 | GSE184371 | GEO

Single-Cell and Spatial Transcriptomics Analysis of Human Adrenal Aging (spatial transcriptomics)

Project description:These data were used in the spatial transcriptomics analysis of the article titled \\"Single-Cell and Spatial Transcriptomics Analysis of Human Adrenal Aging\\".

2024-04-22 | E-MTAB-13991 | biostudies-arrayexpress

Cricket paralysis virus

Project description:Cricket paralysis virus Transcriptome or Gene expression

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Spatial transcriptomics of the axolotl forebrain

Project description:To investigate spatial heterogeneities in the axolotl forebrain, a coronal section of it was obtained for spatial transcriptomics using Visium V1.

2022-07-20 | E-MTAB-11665 | biostudies-arrayexpress

Activation of hypothalaActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseasemic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's diseaseActivation of hypothalamic-enhanced adult-born neurons is sufficient to restore cognitive and noncognitive function in Alzheimer's disease

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

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