Taro Ueno, Jun Tomita, Hiromu Tanimoto, Keita Endo, Kei Ito, Shoen Kume, Kazuhiko Kume. (2012) Identification of a dopamine pathway that regulates sleep and arousal in Drosophila . Nature Neuroscience in press(doi:10.1038/nn.3238)
Sleep is required to maintain physiological functions including memory and is regulated by monoamines across species. Dopamine signal enhancement by dopamine transporter (dDAT) mutation decrease sleep, but the specific pathway is still elusive. Here we show D1 dopamine receptor (dDA1) in the fan-shaped body (FB) is the major target of the arousal effect of dopamine in Drosophila. The short sleep phenotype of the dDAT mutant was completely normalized in the dDAT dDA1 double mutant, but the dDA1 rescue in the dorsal FB resulted in the short sleep phenotype again. In contrast, dDA1 rescue in mushroom body neurons had no effects on sleep, but rescued memory deficit phenotype. The anatomical projection of dopamine neurons to dorsal FB and the physiological effects of dopamine on FB were also confirmed. Finally, using mosaic analysis, a single dopamine neuron projecting to FB was shown to activate arousal. These results elucidated a unique sleep regulating dopamine pathway.
Sleep regulating dopamine pathway
(a) DA neuron projecting fan-shaped body regulates sleep, whereas DA neuron projecting mushroom body regulates memory. Dopamine increases cAMP via D1-like receptor DA1. DA signaling is up-regulated in DAT mutant, fumin .
(b) Sleep regulating dopamine neuron. b1:anterior view 、 b2:posterior view
