Groups of neurons within the spinal cord coordinate the precise movements of locomotive behavior, such as walking or swimming. Our laboratory is interested in the development, organization, and function of these neuronal networks and we use the developing zebrafish as our model system. Zebrafish embryos and larvae have several characteristics that make them particularly well-suited to study spinal cord networks: They demonstrate robust swimming behavior, their spinal cords are relatively simple compared to mammalian spinal cords, the embryos are transparent so spinal cord development can be easily observed, and a large array of genetic resources are available. These features allow us to take an integrated genetic, molecular, cellular, and behavioral approach to study the spinal cord networks that orchestrate locomotive behavior. Since spinal cord organization is broadly conserved among vertebrates, our work holds promise to provide insight into mammalian spinal cords and it provides new models of human disease.

One approach we are taking to examine spinal cord networks utilizes zebrafish mutants that demonstrate abnormal locomotive behavior, indicating that they contain spinal cord network defects. Instead of performing the normal left and right tail flips that comprise swimming behavior, one group of mutants exhibit nose to tail compressions, similar to the accordion musical instrument, and another group of mutants demonstrate uncoordinated, spastic behavior. We are analyzing the cellular and molecular defects in these mutants with the goal of identifying the potentially novel genes and neurons required for locomotive behavior. Complementing this approach, we are also examining the organization and function of GABAergic neurotransmission within the zebrafish spinal cord. GABA is a key neurotransmitter that controls normal locomotive behavior, and we are interested in elucidating the multiple roles it plays during the development of spinal cord networks.