Networks of neurons within the brain and spinal cord coordinate the precise movements of locomotive behavior, such as walking or swimming. My laboratory is interested in the development, organization, and function of these networks and we use the developing zebrafish as our model system. Zebrafish embryos and larvae have several characteristics that make them particularly well-suited as a system to study locomotor networks: They demonstrate robust swimming behavior, their nervous systems are relatively simple compared to mammalian systems, the embryos are optically transparent so internal structures are visible, 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 neural networks that orchestrate locomotive behavior. Since the molecular and cellular mechanisms that control locomotive behavior are often conserved among vertebrate species, our work can provide deeper insight into mammalian systems and furnish new models of human disease.
One approach we have taken to examine the development and function of locomotor networks has been to characterize zebrafish mutants that demonstrate abnormal locomotive behavior, indicating that they contain locomotor 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 an accordion, while another group of mutants demonstrate uncoordinated, spastic behavior. In a complementary approach, we are analyzing the expression and function of genes required for GABA neurotransmission, which is essential for normal locomoter network function. Combined, this work has identified mechanisms essential for brain and spinal cord function and has established new models of several different human disorders, including Maple Syrup Urine Disease (a devastating neurometabolic disorder) and epilepsy. Given that developing zebrafish are small, aquatic, and available in large numbers, these models can now be used for high-throughput small molecule screens to develop new drugs. Our current studies aim to use the resources and insights we have generated to better understand locomotor network development and function, while also developing new therapeutics to combat Maple Syrup Urine Disease and epilepsy.
Learn more at www.bio.umass.edu/biology/downes/
- BS Johnson C. Smith University, 1992
- PhD Washington University, St. Louis, 1999
- Postdoctoral training: University of Pennsylvania, 1999-2005