Functional development of brain-scale neural circuits underlying vertebrate visuomotor transformations

Abstract

Visual behaviors are ubiquitous throughout the animal kingdom, assisting organisms in navigation, reproduction, and survival. The neuronal circuits underlying visual processing change substantially throughout development and adapt throughout life while maintaining proper function. However, the neurobiological mechanisms underlying visual functional circuit maturation remain unknown and largely underexamined. Addressing these questions requires a tractable model system that offers access to all participating neurons and quantifiable visuomotor behaviors across development. This work leverages the genetically and optically tractable zebrafish to monitor the functional maturation of the optomotor response (OMR), an innate visuomotor orienting behavior. This visually guided behavior and the associated neural circuits have been characterized in larval zebrafish older than 6 days post-fertilization. Monitoring OMR behaviors from the moment visual information is provided to the brain at 72 hours post fertilization (hpf), I reveal a stage-like development, uncovering the specific developmental transitions from the immature, non-responsive to a robust OMR repertoire at 120 hpf. To investigate the associated neural circuit maturation, I used two-photon calcium imaging to monitor the activity of nearly all neurons of the OMR circuitry, including the retinorecipient pretectum, revealing distinct region-specific developmental trajectories. Neuronal visual response properties correlate with the developmental stage, explaining behavioral maturation. While sensory neural processing is present in young, 72 hpf zebrafish, lack of hindbrain activation suggests that sensory and motor circuits are not yet connected. Finally, by combining longitudinal imaging with computational cell-tracking methods, I reveal that individual neurons display stable tuning characteristics from 72 hpf onwards, suggesting neurons emerge in specialized circuit roles. These results provide a quantitative framework for advancing our understanding of functional interactions driving visuomotor circuit maturation in vertebrates at the cellular level.