The ability to move within the environment is essential for the survival of all animals, including humans. In mammals, the neurons that generate and drive locomotor movements reside in the spinal cord, and these spinal networks are controlled by upstream signals from the brainstem. Most studies of neural control of locomotion in mammals have focused on straight-trajectory forward locomotion. However, how brainstem and spinal neural networks control turning movements remains poorly understood. This study will investigate this question, using a combination of experimental and computational approaches.
This international CRCNS project will be performed in close colllaboration between Dr. Julien Bouvier (Paris-Saclay University, France) and Drs. Jessica Ausborn and Ilya Rybak (Drexel University). The results of this project will provide important insights into the neural control of turning and, more broadly, the neural control of locomotion. The models developed in this project can serve as test-beds for simulating different aspects of motor disorders and treatment approaches. Study outcomes can help in the development of novel strategies to restore locomotor function after spinal cord injury, neurodegenerative pathologies, and other motor disorders.
This multidisciplinary project will investigate the neural control of locomotion in mice with a focus on mechanisms of turning movements. A recently uncovered population of reticulospinal neurons in the gigantocellular reticular nucleus (Gi) of the brainstem projects to all segments of the spinal cord and is defined by the expression of the transcription factor Chx10 (V2a neurons). Experimentally activating these neurons in the mouse induces robust turning movements that seem to be mostly driven by an asymmetric control of the motor circuits of the neck, upper trunk, and forelimbs. This study will test the hypothesis that these pathways represent a major orchestrator of locomotor turning maneuvers. This study combines state-of-the-art physiological, genetic, pharmacological, and motion tracking approaches with computational modeling of the brainstem and spinal cord circuits and animal biomechanics. The results of in vitro and in vivo studies will be incorporated in a neuro-biomechanical data-driven model of quadrupedal mammalian (mouse) locomotion. The model will provide mechanistic explanations and generate testable predictions that will then be verified experimentally.
The project has the following three objectives. (1) Study the influence of reticulospinal V2a Gi neuron activation on spinal circuits potentially involved in locomotor steering behaviors and computational modeling of these brainstem-spinal pathways and circuits; (2) Characterize kinematics of mouse locomotion during changes of locomotor direction and develop a full-body neuro-biomechanical model of mouse locomotion; (3) Study the role of different populations of reticulospinal V2a Gi neurons in locomotor steering and test model predictions, challenge model assumptions, and investigate general mechanisms.