Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia

Calcagno, B., Eyles, D., van Alphen, B. and van Swinderen, B. (2013) Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia. Translational Psychiatry, 3 e206.1-e206.10. doi:10.1038/tp.2012.139

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Author Calcagno, B.
Eyles, D.
van Alphen, B.
van Swinderen, B.
Title Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia
Journal name Translational Psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1038/tp.2012.139
Open Access Status DOI
Volume 3
Start page e206.1
End page e206.10
Total pages 10
Place of publication London, United Kingdom
Publisher Nature
Language eng
Formatted abstract
It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the “dopamine ontogeny hypothesis of schizophrenia”. To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.
Keyword Brain development
Dopamine
Drosophila
Gamma
Schizophrenia
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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