Cellular Mechanisms of Behavioral Development in the Vestibulospinal Circuit

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PROJECT SUMMARY After birth, animal behaviors mature as neural circuits refine. While the complexity of most neural circuits and their associated behaviors has meant the two are often considered separately, these phenomena are inextricably linked. Revealing how mechanisms of circuit refinement constrain behavioral improvement is critical to understanding brain development in both healthy and diseased states. Balance control is a vital sensorimotor behavior that develops postnatally according to evolutionarily conserved principles across vertebrates. The vestibulospinal circuits that maintain and correct posture also experience developmental refinement, but it is unclear how observed functional and morphological changes translate into improved posture control. The postural reflex circuit in larval zebrafish is an ideal model in which to study how cellular mechanisms of development may instantiate behavioral improvement. As simple vertebrates, zebrafish have a vestibulospinal reflex circuit that functions similarly to mammals. However, the zebrafish circuit consists of orders of magnitude fewer neurons. Our lab's efforts have established genetic and optical means to measure and manipulate neural activity non-invasively with cellular resolution across development. Furthermore, our lab has defined how postural behaviors improve with age in larval zebrafish. We have developed a control theoretic framework to understand the biomechanical underpinnings of this behavioral improvement, and to constrain the neural computations responsible for behavior. In my preliminary work, I have identified a small set of vestibulospinal neurons as a nexus of postural development in the larval fish. The goal of this research proposal is twofold: (1) to leverage the zebrafish vestibulospinal circuit to elucidate cellular mechanisms of circuit development using in vivo longitudinal imaging, and (2) to model how developing neural circuits permit concurrent behavioral improvement. In Aim 1, I will determine how sensory responses in individual vestibulospinal neurons change longitudinally across development. In Aim 2, I will identify how downstream connectivity of vestibulospinal neurons changes both anatomically and functionally during development. In Aim 3, I will adopt a computational approach to relate the encoding and decoding capacity of vestibulospinal activity across development to improvement in postural behaviors. Through the proposed work, I will define hallmarks of sensorimotor circuit development at a cellular level and relate them to their behavioral consequences. When complete, this work will define how neural circuit development gives rise to behavioral improvement.