Grant: Operating Grant

. Locomotion is a basic motor function generated and controlled by genetically defined neuronal networks. The pattern of muscle synergies responsible for locomotor movements is generated in the spinal cord, whereas neural centers located above the spinal cord in the brainstem and brain are essential for initiating and controlling locomotor movements. One such locomotor control center in the brainstem is the Mesencephalic Locomotor Region (MLR), first discovered in cats and later found in all vertebrate species tested to date. Recent studies using functional MRI suggest that this locomotor region is also present in humans and plays a role in locomotion. Such high conservation among vertebrates is a good indication of the key importance of this structure in the functioning of the brain. In animal models, stimulation of the MLR induces locomotion and fine-tunes the power of the locomotor output - somewhat like a rheostat. The cellular mechanisms for this regulation are not yet understood and we propose to analyze this problem. For that purpose, the relative simplicity of the lamprey model is far more favourable than higher vertebrates. We propose to apply an array of neurobiological techniques in the lamprey model to examine how the MLR activates downstream brainstem cells to control locomotion and gate sensory inflow. The information we will gain is fundamental for comprehending how the nervous system initiates and controls locomotor movements. Transposed to mammals, including humans, we believe that this knowledge will be important to elaborate strategies for restoring normal function in patients with motor disorders. An example of knowledge transfer to clinical practice involves Parkinson's patients who show a loss of neurons in the MLR. Electrical stimulation of the MLR has been recently shown to improve locomotion in these patients, an exciting new approach for treatment. It is thus very important to understand better how the MLR regulates locomotion.