A neural center located in the brainstem plays an important role in controlling walking movements. This brainstem centre generates locomotor commands that are sent to the spinal cord, which generates the pattern of muscle contractions. If the brainstem locomotor centre, its targets or the signals it receives are damaged, then severe deficits in the ability to walk appear. A lesion of the spinal cord prevents brainstem commands from reaching the neurons in the spinal cord that produce the locomotor movements. In Parkinson's disease, dopamine neurons die in the brain, resulting in walking deficits. As these dopamine neurons communicate with the brainstem locomotor centre, their loss could severely disrupt the production of locomotor commands.
However, little is known about the functional relationships between the dopamine system, the brainstem locomotor centre and the spinal cord. Using an integrated experimental approach from cell to behavior, my project seeks to identify how the locomotor centre controls the spinal cord and how it is activated by dopamine neurons in salamanders and mice. The salamander swims underwater and walks on ground, which makes it interesting to understand how the locomotor system generates these two behaviors. Moreover, this animal has the extraordinary ability to regenerate its dopamine neurons, and its spinal cord after a complete injury. In parallel, I will use genetically-modified mice that will allow us to characterize at the cellular level how dopamine neurons influence the brainstem locomotor centre using optogenetics.
The project will enable us to gain a more comprehensive understanding of the role of the brainstem in the control of walking in tetrapods. This knowledge will be critical in identifying clinically-relevant targets for people with spinal cord injury, Parkinson's disease, or other movement disorders.