Differential plasticity of excitatory and inhibitory reticulospinal fibers after spinal cord injury: implication for recovery

The remodeling of axonal connections following injury is an important feature driving functional recovery. The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers. While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord, the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear. As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input, we investigated in this study the plastic potential of glutamatergic (vGlut2) and GABAergic (vGat) fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus, two nuclei important for locomotor function. Using a combination of viral tracing, chemogenetic silencing, and AI-based kinematic analysis, we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury, a period prone to neuronal remodeling. We demonstrate that, in this time frame, while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury, vGat-positive fibers are rather unresponsive to injury. We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery. Using kinematic analysis, we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery. Overall, our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.