Monday, November 21, 2022

Scientists Identify Neurons Needed to Walk After Paralysis

Good news! Neurons are phenomenal!

"... The team identified two neural populations that appeared to orchestrate the rewiring of connections between nerve cells following injury in the animal model. ...
In 2018, scientists first recognized that stimulating nerves near the site of injury—a process known as epidural electrical stimulation (EES)—could ease a person’s pain following a spinal cord injury and restore their ability to walk when combined with intensive physical therapy. ...
Specifically, the algorithm identified two subpopulations of excitatory interneurons—nerve cells that connect motor and sensory neurons—that expressed the genetic markers Vsx2 and Hoxa10 as potential drivers of the animals’ recovery. When the scientists applied optogenetics to inactivate these cells, the mice lost their ability to walk again, regaining it only when the cells were activated. In mice without a spinal cord injury, silencing the cells did nothing, suggesting that such cells only become essential to movement following an injury ..."

From the 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 applied during neurorehabilitation (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 sequencingand spatial transcriptomics to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type 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."

Scientists Identify Neurons Needed to Walk After Paralysis | The Scientist Magazine® Nine people with spinal injuries walked again after electrical stimulation, allowing researchers to pinpoint neurons likely underlying their recovery.


Fig. 1: EESREHAB remodels the spinal cord of humans and mice


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