Grant: Operating Grant

Locomotion is a basic motor function of crucial importance for individuals as it allows them to move within their environment. The basic synergy responsible for locomotor movements is generated in the spinal cord, whereas neural centers located in the brain are essential for initiating and controlling locomotion. One such locomotor control center is the Mesencephalic Locomotor Region (MLR) known to be present in all vertebrate species tested to date. Stimulation of the MLR induces locomotion and finely tunes the power of the locomotor output, somewhat like a rheostat. We propose to analyse the cellular mechanisms underlying the MLR control of locomotion in the lamprey. The neural circuitry for locomotion is best known in the lamprey due to the relative simplicity of its nervous system as compared to mammals. In addition, brain structures controlling locomotion in lampreys have a very similar organisation to that of mammals. Using an array of neuroscience techniques, we propose to examine how the MLR activates downstream brainstem cells to control locomotion and how the neural activity in the MLR is controlled by incoming inputs from higher brain structures. The information we will gain is fundamental to understand how the nervous system initiates and controls locomotion; it should translate into better strategies for restoring normal function in patients with motor disorders. Indeed, electrical stimulation of the MLR is presently used to improve walking in Parkinson's disease patients as well as in patients with gait disorders. In addition, it was recently shown that MLR stimulation markedly improves locomotion in rats with a partial spinal lesion. These recent findings may open a whole new strategy for treating spinal cord lesions in humans using MLR stimulation. Because the MLR is now a target for stimulation in humans, it becomes essential to understand how this brain region operates both at system and cellular levels.