Summary description: Deciphering the logic behind how neural circuits generate behavior is a fundamental question in neuroscience. Locomotion offers a unique opportunity to probe issues of neuronal organization because motor circuitry generates a measurable product ? movement. Thus, studies of neural circuits for movement can not only help understand how the nervous system functions in general, but can also help to repair the motor circuitry after it has been disrupted, either by injury or disease. To fully grasp how to address the clinical challenges of overcoming neuronal disease or injury, it is informative to look for solutions in natural processes. This proposal is focused on the fundamental science underlying this transformational vision. The NU team will concentrate on discovering and understanding the function of spinal motor circuitry of a model system: the zebrafish.
Intellectual merit: A major drawback of modern computational models is considered to be that the patterns of connectivity among spinal neurons are largely assumed. With a large parameter space, the assumed neural circuitry in the computational models, that mimic natural behavior, may not be the actual circuitry in organisms. The NU team has designed a research approach based on the hypothesis that information about the required muscle forcing for movement can be used to discover the actual neural circuitry. Hence, instead of assuming any neural circuitry, they propose a novel inverse paradigm in which they will first identify the muscle forcing required to produce the observed swimming kinematics. Second, they will construct possible neural circuits that could lead to the predicted muscle forcing. Finally, they will use transgenic zebrafish lines to hunt for classes of neurons predicted by the modeling, but as yet unidentified. Transformational impact: This project will lead to the discovery of new classes of neurons and the related circuitry, and to a fundamental understanding of how neuronal activation leads to a sequence of events in which the muscle energy is focused and transformed into the translational kinetic energy of movement. These fundamental discoveries and insights will not be restricted to the zebrafish model system but will conceptually apply in general to vertebrates whose movements range from swimming to limbed locomotion.
Broader impact: The PIs will develop new interdisciplinary courses. The work done in this proposal will be a crucial application example that will be introduced in a book on computational methods that the PI is writing. The PI is also developing a novel approach based on computer animation to teach the fundamental principles in his research field. These educational videos will be broadly distributed through the internet by using YouTube.
