The neurons that restore walking after paralysis.

Area of Science:

• Neuroscience
• Regenerative Medicine
• Molecular Biology

Background:

• Spinal cord injury disrupts neural pathways, causing paralysis.
• Epidural electrical stimulation (EES) applied during neurorehabilitation (EES^REHAB) has shown promise in restoring motor function.
• Reduced neuronal activity during EES^REHAB-induced walking suggests a selection of critical neuronal subpopulations.

Purpose of the Study:

• To identify specific neuronal subpopulations essential for regaining walking ability after spinal cord injury.
• To model the mechanisms of EES^REHAB in mice to understand recovery processes.
• To create a molecular atlas of spinal cord recovery.

Main Methods:

• Spatiotemporal epidural electrical stimulation (EES) applied during neurorehabilitation (EES^REHAB).
• Single-nucleus RNA sequencing and spatial transcriptomics in mouse models.
• Cell type and spatial prioritization for neuron identification.

Main Results:

• A specific population of excitatory interneurons in intermediate laminae was identified as crucial for recovery.
• These interneurons are not essential for walking before injury but become vital after injury with EES.
• Augmenting these neurons' activity mimicked EES^REHAB recovery, while ablation prevented it.

Conclusions:

• A distinct subpopulation of excitatory interneurons acts as a 'recovery-organizing center' necessary and sufficient for regaining walking after paralysis.
• The study establishes a framework using molecular cartography to identify neurons driving complex behaviors.
• This research offers a novel approach to understanding and potentially treating paralysis.