Investigating the sleep modulating effect of oxytocin in zebrafish models of autism. (360G-Wellcome-207210_Z_17_Z)

In this project I will test the hypothesis that oxytocin expression and development of oxytocin-expressing neurons are altered in zebrafish with mutations in the ASD risk genes cntnap2 and chd8. I hope to find evidence for the sleep modulating effects of oxytocin, and posit whether deficiencies in oxytocin signalling pathways may contribute to sleep disorders in autism mutants. I will examine oxytocin mRNA levels across the day/night cycle for both wild-type and mutant fish established in the Rihel lab. I will then analyse the pattern of oxytocin expression in the brains of mutant embryos and their wild-type siblings. From the findings in related studies with cntnap2 mutant mice and the Rihel lab zebrafish models of autism (see references [3] and [6]), I expect to see an alteration in the amount of oxytocin mRNA for day/night between the wild-type and mutant embryos, and a change in the number of neurons expressing oxytocin. If such changes are found, they could explain the sleep phenotype observed in cntnap2 autism mutants, and elucidate a link between neuronal circuit dysfunction and behavioural perturbation in this animal model.