title: Transient Dysregulation of Dopamine Signaling in a DevelopingDrosophilaArousal Circuit Permanently Impairs Behavioral Responsiveness in Adults.
abstract: The dopamine ontogeny hypothesis for schizophrenia proposes that transient dysregulation of the dopaminergic system during brain development increases the likelihood of this disorder in adulthood. To test this hypothesis in a high-throughput animal model, we have transiently manipulated dopamine signaling in the developing fruit flyDrosophila melanogasterand examined behavioral responsiveness in adult flies. We found that either a transient increase of dopamine neuron activity or a transient decrease of dopamine receptor expression during fly brain development permanently impairs behavioral responsiveness in adults. A screen for impaired responsiveness revealed sleep-promoting neurons in the central brain as likely postsynaptic dopamine targets modulating these behavioral effects. Transient dopamine receptor knockdown during development in a restricted set of ~20 sleep-promoting neurons recapitulated the dopamine ontogeny phenotype, by permanently reducing responsiveness in adult animals. This suggests that disorders involving impaired behavioral responsiveness might result from defective ontogeny of sleep/wake circuits.
authors.affiliation: Queensland Brain Institute, The University of Queensland , Brisbane, QLD , Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Ferguson
authors.affiliation: Queensland Brain Institute, The University of Queensland , Brisbane, QLD , Australia.
authors.forename: Alice
authors.initials: A
authors.lastname: Petty
authors.affiliation: Queensland Brain Institute, The University of Queensland , Brisbane, QLD , Australia.
authors.forename: Chelsie
authors.initials: C
authors.lastname: Rohrscheib
authors.affiliation: Queensland Brain Institute, The University of Queensland , Brisbane, QLD , Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Troup
authors.affiliation: Queensland Brain Institute, The University of Queensland , Brisbane, QLD , Australia.
authors.forename: Leonie
authors.initials: L
authors.lastname: Kirszenblat
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Queensland Centre for Mental Health Research, Wacol, QLD, Australia.
authors.forename: Darryl W
authors.initials: DW
authors.lastname: Eyles
authors.affiliation: Queensland Brain Institute, The University of Queensland , Brisbane, QLD , Australia.
authors.forename: Bruno
authors.initials: B
authors.lastname: van Swinderen
keywords: D1 receptor; genetics; ontogeny; schizophrenia; sleep; visual