In humans, a severe spinal cord contusion interrupts the vast majority of supraspinal projections to the spinal cord below the lesion. Permanent paralysis results from the chronic failure of these spared projections to engage lumbar circuits producing leg movement. We modeled these injuries in rodents, and showed the immediate access of cortical circuits onto the electrochemically-enabled lumbar spinal cord. Neuroprosthetic rehabilitation leveraged spared motor circuits elements, ultimately leading to the establishment of a cortico-reticulo-spinal relay that mediated the recovery of voluntary control over the legs. Cortical fibers underwent a drastic anatomical remodeling, contacting glutamatergic reticulospinal neurons in the brainstem which, despite lesion variability, consistently retained synaptic connections onto lumbar circuits. This circuit-level reorganization mediated a cortex-dependent recovery of natural locomotor behaviors.
In the aim of refining our understanding of the cortical contribution to the restoration of leg motor control with neuroprosthetic rehabilitation, we established a methodology to translate to rats a technique of endoscopic calcium imaging in freely-moving animals. We increased the stability of the implant, reaching unprecedented chronic degrees of longevity. Using this newly implemented technology, we tracked the activity of single corticolumbar cells during natural walking in intact rats, showing a strong representation of motor behavioral features in the population. We additionally highlighted the stability of locomotion-related classifications of individual neurons, suggesting a segregation of movement-related representations. The contusion was accompanied by important anatomical changes of corticolumbar cell bodies, preventing the longitudinal identification of single neurons across injury. However, population-level analyses highlighted a maintained strong representation of locomotion at late stages after injury and training. We did not find any dynamic change in corticolumbar population activity correlating with the recovery of voluntary leg motor control, which reflected in a stability of the fractions of movement-related neurons. These early results start shedding light on possible mechanisms of functional plasticity accompanying recovery after spinal cord injury, as a peculiar form of motor learning.
Concurrently to the functional reorganization of corticolumbar neurons, we investigated the anatomical plasticity of this specific population with contusion and training. Neuroprosthetic rehabilitation led to a strengthening of collateral connections onto the thoracic spinal segments above the lesion. However, we found no effect of training on the anatomical remodeling throughout the brain and brainstem. Notably, the absence of sprouting of corticolumbar collaterals in the brainstem reticular formation leads us to question the identity of the cortical population involved in the formation of the cortico-reticulo-spinal relay.