AUTHOR=Ferguson Lachlan , Petty Alice , Rohrscheib Chelsie , Troup Michael , Kirszenblat Leonie , Eyles Darryl W. , van Swinderen Bruno 

TITLE=Transient Dysregulation of Dopamine Signaling in a Developing Drosophila Arousal Circuit Permanently Impairs Behavioral Responsiveness in Adults

JOURNAL=Frontiers in Psychiatry

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2017.00022

DOI=10.3389/fpsyt.2017.00022

ISSN=1664-0640

ABSTRACT=<p>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 fly <italic>Drosophila melanogaster</italic> and 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.</p>