The role of heterogeneity among extraocular motor neurons for eye movement control

PROJECT SUMMARY Developmentally-defined subtypes of motor neurons with specialized anatomical and functional properties are required for facilitating movement. Exploring the relationships among developmental, anatomical and functional properties of spinal motor neuron subtypes unveiled fundamental insights into the mechanisms governing locomotion. It is not yet clear to what extent these organizing principles shape motor control outside the spinal cord. Extraocular motor neuron subtypes are similarly anatomically and functionally diverse. Defining the links between development, anatomy, and the role in behavior for individual extraocular motor neurons and how heterogeneity shapes population function is crucial for uncovering the fundamental principles underlying motor system organization. To date, the complexity and developmental inaccessibility of most vertebrate models precludes linking anatomy, birthdate, and function of extraocular motor neurons, thereby limiting our understanding of their individual and collective contributions to behavior. Using the small and accessible model vertebrate – the larval zebrafish – where functional extraocular motor neuron subtypes are genetically accessible therefore provides a unique opportunity to test the hypothesis that general principles organize vertebrate motor systems. Our lab’s previous work links motor neuron pool identity to birthdate and evaluates function by engaging the vestibulo- ocular reflex. My preliminary data indicates that, when mature, extraocular motor neuron responses vary considerably within individual motor pools. The goal of this proposal is to reveal the organization within heterogenous populations of extraocular motor neurons, and to define the behavioral impacts of such variability. Aim 1 will reveal the generality of principles that link developmental, anatomical, and functional properties of individual motor neurons. Aim 2 will define if/how heterogeneity within a population contributes to behavior, illuminating how subtypes of motor neurons work together to control movement. As my long-term goal is to investigate the neural basis of movement in health and disease, this work is foundational training on my path to an independent position. Beyond training, my data stand to speak to the generality of principles of spinal motor circuit organization. Completion of these experiments will take a critical step towards understanding motor system development and function in health and disease.