Neural basis of movement in health and disease

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PROJECT SUMMARY AND ABSTRACT Movement is a fundamental component of behavior that is established and refined throughout development into adulthood. Over the course of a lifetime, our capacity to move is susceptible to neurological disorders and injuries that can pose significant and sometimes fatal risks to human health. This proposal aims to elucidate the underlying molecular mechanisms governing the establishment, maintenance, and adaptation of locomotor behaviors and their disruptions in disease. Utilizing advanced techniques, including genetics, imaging, neuronal tracing, and circuit manipulations, I will investigate motor regulation in awake, behaving animals. My predoctoral and postdoctoral research training will provide a solid foundation for me to become an independent investigator equipped with the knowledge and expertise to uncover essential principles governing motor regulation in health and disease. My predoctoral research focuses on developmental pathways that guide the formation of neural circuits capable of producing rhythmic locomotion. I have chosen the model organism C. elegans for my predoctoral research due to its strengths, including a well-defined time course of development, a collection of powerful genetic tools, a fully resolved connectome, and an array of naturalistic behaviors available for study. Research in Aim 1 (F99 phase) will elucidate the development and regulation of rhythmic locomotion in C. elegans. I hypothesize that individual Wnt pathways have specific roles in programming neural circuits for locomotion and gait transitions in juvenile and adult animals. My predoctoral studies will introduce technical and intellectual innovations to the investigation of locomotor regulation, providing critical insights into the genetic programs necessary for the establishment and maturation of rhythmic locomotion at various developmental stages. In Aim 2 (K00 phase), I will identify a postdoctoral program focusing on mammalian neural circuits for motor control. Research training in the K00 phase will allow me to gain expertise in mouse models of motor regulation and dysfunction. I will work with my supervisory committee and sponsor to identify postdoctoral labs with a supportive environment for my progression into independent research. Upon completion of these Aims, I will have acquired the skills and knowledge to transition into an independent scientist role, where I will conduct foundational research in motor circuit development and regulation, uncovering motor disorder processes and potential therapies.