ABSTRACT
Brain laterality is a prominent feature in Bilateria, where neural functions are favored in a single brain hemisphere. These hemispheric specializations are thought to improve behavioral performance and are commonly observed as sensory or motor asymmetries, such as handedness in humans. Despite its prevalence, our understanding of the neural and molecular substrates instructing functional lateralization is limited. Moreover, how functional lateralization is selected for or modulated throughout evolution is poorly understood. While comparative approaches offer a powerful tool for addressing this question, a major obstacle has been the lack of a conserved asymmetric behavior in genetically tractable organisms. Previously, we described a robust motor asymmetry in larval zebrafish. Following the loss of illumination, individuals show a persistent turning bias that is associated with search pattern behavior with underlying functional lateralization in the thalamus. This behavior permits a simple yet robust assay that can be used to address fundamental principles underlying lateralization in the brain across taxa. Here, we take a comparative approach and show that motor asymmetry is conserved across diverse larval teleost species, which have diverged over the past 200 million years. Using a combination of transgenic tools, ablation, and enucleation, we show that teleosts exhibit two distinct forms of motor asymmetry, vision-dependent and - independent. These asymmetries are directionally uncorrelated, yet dependent on the same subset of thalamic neurons. Lastly, we leverage Astyanax sighted and blind morphs, which show that fish with evolutionarily derived blindness lack both retinal-dependent and -independent motor asymmetries, while their sighted surface conspecifics retained both forms. Our data implicate that overlapping sensory systems and neuronal substrates drive functional lateralization in a vertebrate brain that are likely targets for selective modulation during evolution.
