Developmental Contributions to the Functional Maturation of the Vestibulo-Ocular Reflex

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PROJECT SUMMARY During development, animal behaviors improve as neural circuits refine. Prior work suggests that early developmental events, such as birth timing, define the role a neuron will play in a circuit. However, the complexity of most developing circuits and the behaviors they subserve limit our understanding of the role of early events in circuit maturation. My proposed experiments address this gap by asking if early development shapes circuit maturation. Defining the relationship between development and function is key to understand the how the brain and behavior mature in healthy and diseased states. The larval zebrafish is a particularly tractable model for circuit development due to its genetic accessibility, transparency, and rapid external development. Specifically, the neuronal populations driving gaze stabilization following body tilts in the larval zebrafish are well-conserved and orders of magnitude smaller. Our lab leverages these advantages to link developmental phenomenology with circuit maturation and behavior. We have established genetic and optical means to longitudinally measure and manipulate neural activity across development. Importantly, prior work from our lab has revealed that the birthdate of vestibular neurons influences anatomical location within the brainstem and preferred direction of body tilt. The goal of this proposal is to determine if birthdate similarly predicts how sensory responses mature, and if birthdate predicts a neuron’s contribution to behavior. In Aim 1, I will determine if a central vestibular neuron’s birthdate predicts its sensitivity to body tilts of different magnitudes, and/or how this encoding matures. In Aim 2, I will examine how developmentally and functionally diverse populations of vestibular neurons contribute to behavior using loss- and gain-of-function approaches. My data will define the role of early development in circuit function. Completion of these experiments will speak to the general mechanisms by which circuit function is influenced by – or indifferent to – early development.