The main goal of the proposed research is to understand how the development of hypothalamic neuronal circuits that control complex behaviours such as sleep is disturbed in zebrafish models of autism. For this purpose I will harness a combination of powerful genetic tools available in zebrafish, cutting edge neuroimaging techniques and high-throughput behavioural analysis. The Rihel lab, in collaboration with the Giraldez labs at Yale, has identified diverse sleep/wake phenotypes in zebrafis h mutants harbouring mutations in genes associated with autism. I will test the hypothesis that these sleep phenotypes are due to the altered development and functionality of hypothalamic sleep circuits. I will examine the specification, patterning and connectivity of sleep relevant neuron population located in the hypothalamus, basal forebrain and brain stem using in situ hybridisation, immunostaining and transgenic zebrafish lines. Furthermore, I will image and compare the dynamic activity of developing zebrafish brains of wild-type and mutant larvae to determine the functional integrity of sleep circuits. Differentially active neurons will then be laser-ablated or optogentically/pharmacologically manipulated to directly test their specific sleep/wake circuit function and their contribution to the autism sleep phenotype.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
