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Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine

Nature Neuroscience volume 14, pages 889–895 (2011)Cite this article

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Abstract

How animals maintain proper amounts of sleep yet remain flexible to changes in environmental conditions remains unknown. We found that environmental light suppressed the wake-promoting effects of dopamine in fly brains. The ten large lateral-ventral neurons (l-LNvs), a subset of clock neurons, are wake-promoting and respond to dopamine, octopamine and light. Behavioral and imaging analyses suggested that dopamine is a stronger arousal signal than octopamine. Notably, light exposure not only suppressed l-LNv responses, but also synchronized responses of neighboring l-LNvs. This regulation occurred by distinct mechanisms: light-mediated suppression of octopamine responses was regulated by the circadian clock, whereas light regulation of dopamine responses occurred by upregulation of inhibitory dopamine receptors. Plasticity therefore alters the relative importance of diverse cues on the basis of the environmental mix of stimuli. The regulatory mechanisms described here may contribute to the control of sleep stability while still allowing behavioral flexibility.

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Figure 1: Light suppressed the wake-promoting effects of dopamine.
Figure 2: The l-LNvs form membrane contacts with dopaminergic and octopaminergic neurons.
Figure 3: The l-LNvs responded to dopamine or octopamine application by increasing cAMP.
Figure 4: 12-h light exposure suppressed the responses of l-LNvs to dopamine or octopamine.
Figure 5: The circadian clock (PER) specifically promotes octopamine-induced responses in l-LNvs at night.
Figure 6: Light suppresses dopamine responses by upregulating inhibitory dopamine receptors.

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Acknowledgements

We thank P. Taghert for kindly providing pdfGal4 (X) and UAS-EPAC flies. We obtained UAS-D2R-RNAi lines from the Vienna Drosophila RNAi center. We are grateful to O. Shafer for technical help with cAMP imaging. We also thank E. Dougherty for assistance in confocal microscopy, K. Palm and S. Pescatore for administrative assistance and C. Vecsey for comments on the manuscript. The work was supported in part by grants from the US National Institutes of Health (PO1 NS044232-06 to M.R., R01 MH067284 to L.C.G. and NIH R01 EB007042 to P. Hong).

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Authors and Affiliations

  1. Howard Hughes Medical Institute, National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts, USA

    Yuhua Shang, Fang Guo & Michael Rosbash

  2. Department of Biology, Brandeis University, Waltham, Massachusetts, USA

    Yuhua Shang, Paula Haynes, Nicolás Pírez, Fang Guo, Leslie C Griffith & Michael Rosbash

  3. Department of Computer Science, Brandeis University, Waltham, Massachusetts, USA

    Kyle I Harrington, Jordan Pollack & Pengyu Hong

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  1. Yuhua Shang
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Contributions

Y.S. conceived the project. Y.S., P. Haynes, N.P. and F.G. performed the experiments. K.I.H., J.P. and P. Hong developed the algorithm for the automated imaging analysis. Y.S., L.C.G. and M.R. wrote the paper.

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Correspondence to Michael Rosbash.

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Shang, Y., Haynes, P., Pírez, N. et al. Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine. Nat Neurosci 14, 889–895 (2011). https://doi.org/10.1038/nn.2860

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