Brainstem and spinal mechanisms of gait transition in a limbed vertebrate

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A striking feature of locomotor control is the ability to switch between locomotor modes (walking, swimming, flying). In vertebrates, the Mesencephalic Locomotor Region (MLR) plays an important role in locomotor control. MLR stimulation initiates locomotion and increasing stimulation intensity increases locomotor speed and elicits gait transitions. The MLR projects to reticulospinal cells that activate the spinal locomotor networks. Much of what we know about this circuitry was obtained in a fish, the lamprey. However, in limbed vertebrates, how this circuitry controls gait transitions is unknown. ******My long-term goal is to identify the role of brainstem and spinal cells in gait transition using a combination of approaches including electrophysiology, calcium imaging, neuroanatomy and movement analysis in salamanders. These tetrapods are ideal to study the neural mechanisms underlying gait transition, as they swim underwater and walk on ground. In semi-intact preparations where the brain is exposed and the body is free to move, low MLR stimulation intensities evoke walking, whereas higher intensities evoke swimming. ***My research program for the next 5 years contains 2 specific projects: ***1) Mechanisms through which MLR cells activate reticulospinal nuclei during walking and swimming. We will identify MLR projections to reticulospinal nuclei using tracing and immunofluorescence. Connectivity will be validated by recording MLR-evoked responses in reticulospinal cells using electrophysiology and calcium imaging. The behavioural role of this connectivity will be identified by deactivating MLR inputs to reticulospinal nuclei in semi-intact preparations. A Ph.D. student will be in charge of this project.***2) Mechanisms through which reticulospinal cells control axial and limb spinal circuits. We will identify the reticulospinal projections to axial and limb spinal cells using tracing and immunofluorescence. The responses evoked by reticulospinal stimulation in axial and limb motoneurons will be recorded using electrophysiology and calcium imaging. We will determine whether different spinal cells are recruited when increasing MLR stimulation. Two master's students will be involved in the project. Undergraduate students will contribute to both projects. ******The new knowledge will provide a more comprehensive view of the role of brainstem cells and their spinal targets in gait transition in tetrapods. It will serve for developing innovative brain-machine interfaces to control locomotor devices in collaboration with Pr. A.J. Ijspeert (École Polytechnique FÉdÉrale de Lausanne). My research approach will provide an integrated training framework preparing highly qualified personnel for careers in basic research or research applied to clinical or bioengineering fields.