Motor Behavior and Epilepsy
Our research has two, closely related goals. One goal is to better understand how genes and neural networks in the brain and spinal cord control movement. More recently, we’ve establish a second goal, which is provide new insight into epilepsy and develop new therapeutics to treat these disorders. To pursue both of our research goals we use zebrafish. Developing zebrafish have several features that make it a great model system. The embryos and larvae develop quickly, exhibit strong motor behavior, are transparent so their brains can be easily observed, and we can use the power of zebrafish genetics to investigate how genes regulate nervous system function. These features allow us to take an integrated genetic, microscopic imaging, and behavioral approach to study the neural networks that control movement. Since many genes and aspects of brain function are conserved among vertebrates, developing zebrafish offer many advantages to model genetic epilepsies, investigate how neural networks are disrupted to cause seizures, and establish high-throughput platforms to identify new therapeutic strategies.
de Soysa, Y.T., Ulrich, A., Friedrich, T., Pite, D., Compton, S., Ok, D., Bernardos, R.L., Hsieh, S., Downes, G.B., Rachael Stein, Lagdameo, M.C., Halvorsen, K., and Barresi, M.J.F. 2012. Macondo crude oil from the Deepwater Horizon oil spill disrupts specific developmental processes during zebrafish embryogenesis. BMC Biology, 10: 40.
Khan, T.M., Benaich, N., Malone, C.F., Bernandos, R.L., Russell, A.R., Downes, G.B., Barresi, M.J., and Hutson, L.D. 2012. Vincrisitne and bortezomib cause axon outgrowth and behavioral defects in larval zebrafish. Journal of the Peripheral Nervous System, 17: 76-89.
Friedrich, T., Lambert, A.M., Masino, M.A., and Downes, G.B. 2012. Mutation of zebrafish dihydrolipoyl transacylase results in abnormal motor behavior and models maple syrup urine disease. Disease Models and Mechanisms, 5: 248-58.
McKeown, K.A., Moreno, R., Hall, V.L., Ribera, A.B., and Downes, G.B. 2012. Zebrafish technotrouser mutants demonstrate abnormal locomotive behavior development due to mutation of a glutamate transporter. Developmental Biology, 362: 162-71.
Olson, B.D., Sgourdou, P., and Downes, G.B. 2010. Analysis of a zebrafish behavioral mutant reveals a dominant mutation in atp2a1/SERCA1. Genesis, 48: 354-61.
McKeown, K.A., Downes, G.B., and Hutson, L.D. 2009. Modular Laboratory Exercises to analyze the development of zebrafish motor behavior. Zebrafish, 6: 179-85.
Downes, G.B. and Granato, M. 2006. Supraspinal input is not required to generate glycine-mediated locomotive behaviors in the zebrafish embryo. J. Neurobiology, 66: 437-51.
Hiromi, H., Saint-Amant, L., Downes, G.B., Cui, W.W., Zhou, W., Granato, M., Kuwada, J.Y. 2005. Zebrafish bandoneon mutants display behavioral defects due to a mutation in the glycine receptor beta subunit. P.N.A.S., 102: 8345-50.
Downes, G.B. and Granato, M. 2004. Acetylcholinesterase function is dispensable for neurite growth but is critical for neuromuscular synapse stability. Developmental Biology, 270: 232-45.
Downes, G.B., Waterbury, J.A., and Granato, M. 2002. Rapid in vivo labeling of identified zebrafish neurons. Genesis, 34: 196-202.
Downes, G.B. and Gautam, N. 1999. The G protein subunit gene families. Genomics, 62: 447-55.
Downes, G.B., Gilbert, D.J., Copeland, N.G., Gautam, N. and Jenkins, N.A. 1999. Chromosomal mapping of five mouse G protein g subunits. Genomics, 57: 173-6.
Downes, G.B., Copeland, N., Jenkins, N.A., and Gautam, N. 1998. Structure And mapping of the G protein gamma3 subunit gene and a divergently transcribed novel gene, Gng3lg. Genomics, 15: 220-30.
Gautam, N., Downes, G.B., Yan, K., and Kisselev, O. 1998. The G protein beta-gamma complex. Cell Signal, 10: 447-55.