Grant: Project Grant

Spinal cord injury can lead to long-lasting loss of leg movements. My previous work has shown that eliminating a population of spinal neurons, known as dI3 neurons, compromises the recovery of walking through treadmill training after a complete spinal transection in mice. Preliminary data from the lab suggest that exciting dI3 neurons in mice with complete spinal transections facilitates recovery of locomotion. These experiments, following complete transection, allowed us to study mechanisms contained entirely within the spinal cord. To further understand the potential for targeting dI3 neurons in human spinal cord injury patients, we now seek to study the impact of stimulating dI3 neurons by studying mice with spinal cord contusion injuries, which more closely model injuries in the human population. The proposal's first aim is to test the impact of pharmacologically silencing dI3 neurons in mice with spinal cord contusion injuries. The second aim will test whether pharmacological stimulation of dI3 neurons can improve the recovery of locomotor function in mice with spinal cord contusion injuries. The final aim will test whether the precise activation of dI3 neurons using light-based excitation can further improve the recovery of locomotor function in mice with spinal cord contusion injuries. This technical approach enables us to test whether stimulating dI3 neurons at precise times during walking can further enhance the recovery of locomotion. To achieve these aims, behavioural analysis in combination with muscle recordings will allow us to gain insight into the role of dI3 neurons using transgenic mouse models designed in my lab to target dI3 neurons. The study of these neurons in the recovery of motor function after spinal cord contusion injuries will be an essential step in developing new therapeutic strategies for prolonged improvement of locomotor function following more common spinal cord injuries in the human population.