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Biologists have discovered a population of cells that provides a therapeutic effect of electrical stimulation in paralysis

Anna Muravyeva, N+1

The work of only one subpopulation of spinal cord neurons helped patients with paralysis to move again. For the treatment of spinal cord injuries, the authors of an article published in Nature (Kathe et al., The neurons that restore walking after paralysis) used electrical stimulation of lumbar cells. It turned out that the effect of this therapy is based on the activation of one subpopulation of SC Vsx2 interneuron ^{cells::Hoxa10}, who did not even participate in walking before paralysis.

The neurons that control walking are located in the lumbar region of the spinal cord – they transmit signals from the brainstem to the muscles, causing them to contract. Spinal cord injuries disrupt this complex network of neural connections and can cause paralysis and complete inability to move. 

Recent studies have shown that epidural electrical stimulation is able to restore movement after spinal cord injury — for such therapy, patients are implanted in the spinal cord with a small generator of electrical impulses that sends a signal to the posterior roots of the lumbar spinal cord.

Stimulation allows immediate restoration of motor network function and allows patients to walk again. However, the biological principles by which such therapy works have not yet been investigated.

Scientists from the Federal Polytechnic School of Lausanne, led by Claudia Kathe, suggested that electrical stimulation affects yet unexplored neurons that begin to participate in walking only when recovering from paralysis. This hypothesis was supported by the data obtained by scientists — in a clinical trial of therapy, neural activity in the lumbar segments of the spinal cord fell, not increased. This suggested that another group of neurons, which does not perform a routine motor function, is engaged in restoring activity after paralysis.

To test this hypothesis, the researchers created a mouse model of spinal cord injury, as well as a therapeutic system of stimulation and mechanical support of body weight when walking. To investigate how mouse neurons respond to therapy, scientists have created an entire atlas of cells based on their gene expression and location in the spinal cord. To do this, biologists used RNA sequencing in each of the cell nuclei separately (snRNA-seq) and applied the sequencing results to the projection of the spinal cord. So it was possible to identify 36 subpopulations based on the work of marker genes.

To identify the subpopulation that the researchers were looking for (taking part in rehabilitation), biologists used the prioritization method. The Augur machine learning algorithm identified in the constructed atlas those neurons whose expression changed most during rehabilitation. It turned out that there is a group of neurons that changes its expression in response to all the parameters of therapy. These cells expressed markers Vsx2 and Hoxa10 and belonged to the group of excitatory interneurons. They were named after these genes and origin from the spinal cord (spinal cord) – SC ^Vsx2::Hoxa10.

Next, the researchers checked whether these cells really take part in routine walking before injury and in the rehabilitation process itself. To do this, in both cases, the activity of the cells was artificially suppressed and checked how this affected the movements. It turned out that this subpopulation is not needed for walking a healthy animal – its shutdown did not affect it. But for recovery during electrostimulation therapy, SCVsx2 cells::Hoxa10 proved to be critically important.

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