Transient dysregulation of dopamine signaling in a developing drosophila arousal circuit permanently impairs behavioral responsiveness in adults

Ferguson, Lachlan, Petty, Alice, Rohrscheib, Chelsie, Troup, Michael, Kirszenblat, Leonie, Eyles, Darryl W. and van Swinderen, Bruno (2017) Transient dysregulation of dopamine signaling in a developing drosophila arousal circuit permanently impairs behavioral responsiveness in adults. Frontiers in Psychiatry, 8 FEB: . doi:10.3389/fpsyt.2017.00022


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 name Frontiers in Psychiatry   Check publisher's open access policy
ISSN 1664-0640
Publication date 2017-02-13
Sub-type Article (original research)
DOI 10.3389/fpsyt.2017.00022
Open Access Status DOI
Volume 8
Issue FEB
Total pages 14
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2018
Language eng
Formatted 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.
Keyword Schizophrenia
Ontogeny
Sleep
Visual
D1 receptor
Genetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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