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Identification of a dopamine pathway that regulates sleep and arousal in Drosophila


Sleep is required to maintain physiological functions, including memory, and is regulated by monoamines across species. Enhancement of dopamine signals by a mutation in the dopamine transporter (DAT) decreases sleep, but the underlying dopamine circuit responsible for this remains unknown. We found that the D1 dopamine receptor (DA1) in the dorsal fan-shaped body (dFSB) mediates the arousal effect of dopamine in Drosophila. The short sleep phenotype of the DAT mutant was completely rescued by an additional mutation in the DA1 (also known as DopR) gene, but expression of wild-type DA1 in the dFSB restored the short sleep phenotype. We found anatomical and physiological connections between dopamine neurons and the dFSB neuron. Finally, we used mosaic analysis with a repressive marker and found that a single dopamine neuron projecting to the FSB activated arousal. These results suggest that a local dopamine pathway regulates sleep.

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Figure 1: DA1 mediates the wake-promoting effects of dopamine.
Figure 2: DA1 in the FSB, but not in the mushroom body, mediates the wake-promoting effects of dopamine.
Figure 3: Activation of the dFSB induces sleep in control and DATfmn flies.
Figure 4: Ablation of PDF neurons does not eliminate the arousal effect of dopamine.
Figure 5: The FSB neuron is anatomically connected to a dopamine neuron.
Figure 6: The FSB neurons show a response to dopamine.
Figure 7: The activation of dopamine neurons by TrpA1 resulted in a reduction in sleep.
Figure 8: Activation of an FSB-projecting PPM3 dopamine neuron was sufficient to decrease sleep.


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We thank M. Wu and Q. Liu for sharing unpublished results, K. Ueno, T. Sakai and S. Sato for encouraging advice, M. Yamazaki, A. Miyoshi, Y. Kawahara and W. Honghang for technical assistance, F.W. Wolf for the kind gift of an antibody, R. Jackson and the members of Kume laboratory for discussion and critical reading of the manuscript, and P. Garrity, D. Armstrong, J. Hirsh, K. Scott, the Kyoto Drosophila Genetic Resource Center and the Bloomington Stock Center for fly stocks. This work was supported by a grant (22300132) from the Japanese Society for the Promotion of Science (JSPS). T.U. is a JSPS fellow. S.K. is a member of the Global COE Program (Cell Fate Regulation Research and Education Unit).

Author information




T.U. and K.K. designed the study. T.U. performed the experiments and data analysis. J.T., H.T., K.E. and K.I. contributed unpublished reagents. H.T., S.K. and K.K. directed the study. T.U., J.T., H.T., K.E., K.I., S.K. and K.K. wrote the manuscript.

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Correspondence to Kazuhiko Kume.

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The authors declare no competing financial interests.

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Supplementary Text and Figures

Supplementary Figures 1–10 (PDF 3371 kb)

Supplementary Video 1

This file contains a movie showing labeling of 104y-GAL4 and Nv131-LexA in the central brain in reference to Figure 5a. Green indicates CD2::GFP driven by Nv131-LexA. Magenta indicates mCD8::RFP driven by 104y-GAL4. (AVI 2156 kb)

Supplementary Video 2

This file contains a movie showing labeling of Nv131-LexA with anti-TH immunostaining in reference to Figure 5b. Green indicates CD2::GFP driven by Nv131-LexA. Magenta indicates immunostaining of dopamine neurons with the anti-TH antibody. (MOV 1766 kb)

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Ueno, T., Tomita, J., Tanimoto, H. et al. Identification of a dopamine pathway that regulates sleep and arousal in Drosophila. Nat Neurosci 15, 1516–1523 (2012).

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