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The Journal of Neuroscience, August 10, 2005, 25(32):7377-7384; doi:10.1523/JNEUROSCI.2048-05.2005

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Cellular/Molecular
Dopamine Is a Regulator of Arousal in the Fruit Fly

Kazuhiko Kume,^1,2 Shoen Kume,¹ Sang Ki Park,³ Jay Hirsh,³ and F. Rob Jackson²

¹Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan, ²Department of Neuroscience, Center for Neuroscience Research, Tufts University School of Medicine, Boston, Massachusetts 02111, and ³Department of Biology, University of Virginia, Charlottesville, Virginia 22904-4328

Sleep and arousal are known to be regulated by both homeostatic and circadian processes, but the underlying molecular mechanisms are not well understood. It has been reported that the Drosophila rest/activity cycle has features in common with the mammalian sleep/wake cycle, and it is expected that use of the fly genetic model will facilitate a molecular understanding of sleep and arousal. Here, we report the phenotypic characterization of a Drosophila rest/activity mutant known as fumin (fmn). We show that fmn mutants have abnormally high levels of activity and reduced rest (sleep); genetic mapping, molecular analyses, and phenotypic rescue experiments demonstrate that these phenotypes result from mutation of the Drosophila dopamine transporter gene. Consistent with the rest phenotype, fmn mutants show enhanced sensitivity to mechanical stimuli and a prolonged arousal once active, indicating a decreased arousal threshold. Strikingly,fmn mutants do not show significant rebound in response to rest deprivation as is typical for wild-type flies, nor do they show decreased life span. These results provide direct evidence that dopaminergic signaling has a critical function in the regulation of insect arousal.

Key words: sleep; rest; arousal; Drosophila; dopamine; dopamine transporter

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Received April 15, 2005; revised June 25, 2005; accepted June 30, 2005.

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