Grant: Project Grant

Spinal cord injury can lead to long-lasting loss of leg movements. My previous work has demonstrated the importance of a population of spinal neurons, named dI3 interneurons, in recovery from spinal cord injury. Preliminary data from the lab suggests that these dI3 interneurons may facilitate recovery through treadmill training by two mechanisms. First, dI3 interneurons may generate the muscle tone necessary for treadmill training to be effective. Secondly, dI3 interneurons may be involved in coordinating the leg's flexor and extensor muscles required for everyday walking. The proposal's first aim will show that turning off dI3 interneurons after spinal cord injury removes muscle tone and prevents treadmill training from being effective. In contrast, we will show that increasing the activity of dI3 interneurons improves walking through treadmill training. The second aim will be to demonstrate that dI3 interneurons facilitate muscle tone in injured animals. We propose a series of experiments where activation of dI3 interneurons leads to muscle activity patterns in the limbs that generate weight support. Our final aim will test whether dI3 interneurons facilitate a stepping reflex that could be useful for promoting the recovery of locomotion. We will use muscle recordings and nerve stimulation to test the effects of inhibiting and exciting dI3 interneurons on the stepping reflex in injured animals. To achieve these aims, we will use novel technology allowing select neurons to be turned on or off through orally administered compounds in a mouse model of spinal cord injury. Behavioural analysis in combination with muscle recordings during behaviour will allow us to gain insight into the role of dI3 interneurons in the recovery of motor function after injury. This work will be an essential step in developing new therapeutic strategies for prolonged improvement of locomotor function following spinal cord injury.