Title |
Transient Dysregulation of Dopamine Signaling in a Developing Drosophila Arousal Circuit Permanently Impairs Behavioral Responsiveness in Adults
|
---|---|
Published in |
Frontiers in Psychiatry, February 2017
|
DOI | 10.3389/fpsyt.2017.00022 |
Pubmed ID | |
Authors |
Lachlan Ferguson, Alice Petty, Chelsie Rohrscheib, Michael Troup, Leonie Kirszenblat, Darryl W. Eyles, Bruno van Swinderen |
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 fly Drosophila melanogaster 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. |
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