Although neurodevelopmental disorders such as autism and schizophrenia are associated with disrupted sleep, the extent to which sleep-regulating circuits are disrupted by these diseases is unknown. Similarly, it is unclear how altered sleep influences disease progression and symptoms. The combination of new genome editing techniques with advances in neuronal imaging and behavioral pharmacology makes the larval zebrafish an excellent model system to investigate normal and mutant sleep circuits. This project will generate zebrafish harboring mutations in neurodevelopmental disease genes, assess a series of normal and drug-induced sleep and locomotor phenotypes, and examine developmental changes to sleep circuits.
McCarroll, S.A., and Hyman, S.E. (2013). Progress in the genetics of polygenic brain disorders: significant new challenges for neurobiology. Neuron 80, 578–587.
Hirata, H., Ogino, K., Yamada, K., Leacock, S., and Harvey, R.J. (2013). Defective escape behavior in DEAH-box RNA helicase mutants improved by restoring glycine receptor expression. J. Neurosci. 33, 14638–14644
Rihel J, and Schier AF (2013). Sites of action of sleep and wake drugs: insights from model organisms. Current Opinion in Neurobiology, 23(5):831-40.
Rihel J, and Schier AF (2012). Behavioral screening for neuroactive drugs in zebrafish. Developmental Neurobiology, 72(3):373-385.
Rihel J*, Prober DA*, Arvanites A, Lam K, Jang S, Haggarty SJ, Kokel D, Rubin LL, Peterson RT, and Schier AF (2010). Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science, 327(5963):348-51.