PROJECT SUMMARY Abstract The refinement of gross motor skills, such as locomotion, during development is conserved across vertebrate species. As an example, locomotor output produced by immature animals is initially coarse and becomes progressively more refined during development. Although we previously demonstrated, in larval zebrafish, that neuromodulatory signaling via the dopaminergic system was necessary for the developmental transformation of locomotor (swimming) activity from an immature to a mature state, the underlying molecular and functional mechanisms remain elusive. Our goal here is to characterize the functional and molecular mechanisms underlying the dopaminergic-mediated refinement of spinal locomotor activity using an established vertebrate model system (larval zebrafish) and a well-validated complement of tools, including electrophysiology, pharmacology, in vivo functional imaging (calcium and dopamine), and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results of this project will serve as the basis for a future R01 proposal that will examine the causal relationship between the developmental changes in the dopaminergic system and locomotor refinement. Overall, since the dopaminergic and motor systems are highly conserved across vertebrates, we expect these findings to translate to other animals, including humans.