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Layered reward signalling through octopamine and dopamine in Drosophila

Nature volume 492, pages 433–437 (2012)Cite this article

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Abstract

Dopamine is synonymous with reward and motivation in mammals1,2. However, only recently has dopamine been linked to motivated behaviour and rewarding reinforcement in fruitflies3,4. Instead, octopamine has historically been considered to be the signal for reward in insects5,6,7. Here we show, using temporal control of neural function in Drosophila, that only short-term appetitive memory is reinforced by octopamine. Moreover, octopamine-dependent memory formation requires signalling through dopamine neurons. Part of the octopamine signal requires the α-adrenergic-like OAMB receptor in an identified subset of mushroom-body-targeted dopamine neurons. Octopamine triggers an increase in intracellular calcium in these dopamine neurons, and their direct activation can substitute for sugar to form appetitive memory, even in flies lacking octopamine. Analysis of the β-adrenergic-like OCTβ2R receptor reveals that octopamine-dependent reinforcement also requires an interaction with dopamine neurons that control appetitive motivation. These data indicate that sweet taste engages a distributed octopamine signal that reinforces memory through discrete subsets of mushroom-body-targeted dopamine neurons. In addition, they reconcile previous findings with octopamine and dopamine and suggest that reinforcement systems in flies are more similar to mammals than previously thought.

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Figure 1: Octopamine mediates the short-term reinforcing effects of sweet taste.
Figure 2: Octopamine neuron stimulation can replace sugar presentation during conditioning to form short-term appetitive memory.
Figure 3: Reinforcing dopamine neurons are functionally downstream of octopamine-dependent reinforcement.
Figure 4: Octopamine-dependent reinforcement functions through discrete groups of dopamine neurons.

References

  1. Dayan, P. & Balleine, B. W. Reward, motivation, and reinforcement learning. Neuron 36, 285–298 (2002)

    Article  CAS  Google Scholar 

  2. Wise, R. A. Dopamine, learning and motivation. Nature Rev. Neurosci. 5, 483–494 (2004)

    Article  CAS  Google Scholar 

  3. Krashes, M. J. et al. A neural circuit mechanism integrating motivational state with memory expression in Drosophila . Cell 139, 416–427 (2009)

    Article  CAS  Google Scholar 

  4. Liu, C. et al. A subset of dopamine neurons signals reward for odour memory in Drosophila . Nature 488, 512–516 (2012)

    Article  ADS  CAS  Google Scholar 

  5. Hammer, M. An identified neuron mediates the unconditioned stimulus in associative olfactory learning in honeybees. Nature 366, 59–63 (1993)

    Article  ADS  CAS  Google Scholar 

  6. Hammer, M. & Menzel, R. Multiple sites of associative odour learning as revealed by local brain microinjections of octopamine in honeybees. Learn. Mem. 5, 146–156 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Schwaerzel, M. et al. Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila . J. Neurosci. 23, 10495–10502 (2003)

    Article  CAS  Google Scholar 

  8. Cole, S. H. et al. Two functional but noncomplementing Drosophila tyrosine decarboxylase genes: distinct roles for neural tyramine and octopamine in female fertility. J. Biol. Chem. 280, 14948–14955 (2005)

    Article  CAS  Google Scholar 

  9. Monastirioti, M., Linn, C. E. J. & White, K. Characterization of Drosophila tyramine beta-hydroxylase gene and isolation of mutant flies lacking octopamine. J. Neurosci. 16, 3900–3911 (1996)

    Article  CAS  Google Scholar 

  10. Kitamoto, T. Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. J. Neurobiol. 47, 81–92 (2001)

    Article  CAS  Google Scholar 

  11. Burke, C. J. & Waddell, S. Remembering nutrient quality of sugar in Drosophila . Curr. Biol. 21, 746–750 (2011)

    Article  CAS  Google Scholar 

  12. Fujita, M. & Tanimura, T. Drosophila evaluates and learns the nutritional value of sugars. Curr. Biol. 21, 751–755 (2011)

    Article  CAS  Google Scholar 

  13. Hamada, F. N. et al. An internal thermal sensor controlling temperature preference in Drosophila . Nature 454, 217–220 (2008)

    Article  ADS  CAS  Google Scholar 

  14. Busch, S., Selcho, M., Ito, K. & Tanimoto, H. A map of octopaminergic neurons in the Drosophila brain. J. Comp. Neurol. 513, 643–667 (2009)

    Article  Google Scholar 

  15. Heisenberg, M. Mushroom body memoir: from maps to models. Nature Rev. Neurosci. 4, 266–275 (2003)

    Article  CAS  Google Scholar 

  16. Kim, Y. C., Lee, H. G. & Han, K. A. D1 dopamine receptor dDA1 is required in the mushroom body neurons for aversive and appetitive learning in Drosophila . J. Neurosci. 27, 7640–7647 (2007)

    Article  CAS  Google Scholar 

  17. Gohl, D. M. et al. A versatile in vivo system for directed dissection of gene expression patterns. Nature Methods 8, 231–237 (2011)

    Article  CAS  Google Scholar 

  18. Claridge-Chang, A. et al. Writing memories with light-addressable reinforcement circuitry. Cell 139, 405–415 (2009)

    Article  CAS  Google Scholar 

  19. Aso, Y. et al. Specific dopaminergic neurons for the formation of labile aversive memory. Curr. Biol. 20, 1445–1451 (2010)

    Article  CAS  Google Scholar 

  20. Mao, Z. & Davis, R. L. Eight different types of dopaminergic neurons innervate the Drosophila mushroom body neuropil: anatomical and physiological heterogeneity. Front. Neural Circuits 3, 5 (2009)

    Article  Google Scholar 

  21. Han, K. A., Millar, N. S. & Davis, R. L. A novel octopamine receptor with preferential expression in Drosophila mushroom bodies. J. Neurosci. 18, 3650–3658 (1998)

    Article  CAS  Google Scholar 

  22. Balfanz, S., Strunker, T., Frings, S. & Baumann, A. A family of octopamine receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogaster . J. Neurochem. 93, 440–451 (2005)

    Article  CAS  Google Scholar 

  23. Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods 6, 875–881 (2009)

    Article  CAS  Google Scholar 

  24. Maqueira, B., Chatwin, H. & Evans, P. D. Identification and characterization of a novel family of Drosophila beta-adrenergic-like octopamine G-protein coupled receptors. J. Neurochem. 94, 547–560 (2005)

    Article  CAS  Google Scholar 

  25. Crocker, A. & Sehgal, A. Octopamine regulates sleep in Drosophila through protein kinase A-dependent mechanisms. J. Neurosci. 28, 9377–9385 (2008)

    Article  CAS  Google Scholar 

  26. Waddell, S. Dopamine reveals neural circuit mechanisms of fly memory. Trends Neurosci. 33, 457–464 (2010)

    Article  CAS  Google Scholar 

  27. Feinberg, E. H. et al. GFP reconstitution across synaptic partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron 57, 353–363 (2008)

    Article  CAS  Google Scholar 

  28. Gordon, M. D. & Scott, K. Motor control in a Drosophila taste circuit. Neuron 61, 373–384 (2009)

    Article  CAS  Google Scholar 

  29. Pitman, J. L. et al. A pair of inhibitory neurons are required to sustain labile memory in the Drosophila mushroom body. Curr. Biol. 21, 855–861 (2011)

    Article  CAS  Google Scholar 

  30. Koon, A. C. et al. Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling. Nature Neurosci. 14, 190–199 (2011)

    Article  CAS  Google Scholar 

  31. Lee, H. G., Seong, C. S., Kim, Y. C., Davis, R. L. & Han, K. A. Octopamine receptor OAMB is required for ovulation in Drosophila melanogaster . Dev. Biol. 264, 179–190 (2003)

    Article  CAS  Google Scholar 

  32. Lai, S. L. & Lee, T. Genetic mosaic with dual binary transcriptional systems in Drosophila. Nature Neurosci. 9, 703–709 (2006)

    Article  CAS  Google Scholar 

  33. Dietzl, G. et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila . Nature 448, 151–156 (2007)

    Article  ADS  CAS  Google Scholar 

  34. Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451–461 (1999)

    Article  CAS  Google Scholar 

  35. Wagh, D. A. et al. Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila . Neuron 49, 833–844 (2006)

    Article  CAS  Google Scholar 

  36. Nicolaï, L. J. J. et al. Genetically encoded dendritic marker sheds light on neuronal connectivity in Drosophila . Proc. Natl Acad. Sci. USA 107, 20553–20558 (2010)

    Article  ADS  Google Scholar 

  37. Yoshihara, M. Simultaneous recording of calcium signals from identified neurons and feeding behavior of Drosophila melanogaster . J. Vis. Exp. 62, e3625 (2012)

    Google Scholar 

Download references

Acknowledgements

We are grateful to M. Yoshihara, S. DasGupta, V. Budnik and S. Goodwin for reagents. We thank T. Clandinin and E. Kravitz for collegial exchange. D.O. was supported by an EMBO Long-Term Fellowship and a Sir Henry Wellcome Postdoctoral Fellowship. D.G. was supported by a Ruth L. Kirschstein NRSA Postdoctoral Fellowship (F32EY020040). M.S. was supported by a Jane Coffin Childs Postdoctoral Fellowship. S.W. is funded by a Wellcome Trust Senior Research Fellowship in the Basic Biomedical Sciences, by grants MH069883 and MH081982 from the National Institutes of Health and by funds from the Gatsby Charitable Foundation and Oxford Martin School.

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Author notes

  1. Michael J. Krashes

    Present address: Present address: Beth Israel Deaconess Medical Center, Harvard Medical School, Center for Life Sciences, 3 Blackfan Circle, Boston, Massachusetts 02215, USA.,

  2. Christopher J. Burke and Wolf Huetteroth: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA,

    Christopher J. Burke, Michael J. Krashes & Scott Waddell

  2. Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK ,

    Wolf Huetteroth, David Owald, Emmanuel Perisse, Gaurav Das & Scott Waddell

  3. Department of Neurobiology, Stanford University, Stanford, 94305, California, USA

    Daryl Gohl & Marion Silies

  4. Division of Biological Sciences and Center for Structural and Functional Neuroscience, University of Montana, Missoula, 59812, Montana, USA

    Sarah Certel

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Contributions

S.W., C.J.B. and W.H. conceived this project and designed all experiments. C.J.B. and W.H. constructed fly strains, C.J.B. performed most behaviour, with some assistance from E.P. Anatomical data were produced by W.H. and C.B. Live imaging was performed by D.O. and W.H. The study was initiated by the experiments of M.J.K. G.D. constructed lexAop-dTrpA1. The 0104-, 0273-, 0665- and 0891-GAL4 flies were generated and initially characterized by D.G. and M.S. S.C. constructed and initially characterized Tdc2-lexA flies. S.W., W.H. and C.B. wrote the manuscript.

Corresponding author

Correspondence to Scott Waddell.

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The authors declare no competing financial interests.

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Burke, C., Huetteroth, W., Owald, D. et al. Layered reward signalling through octopamine and dopamine in Drosophila. Nature 492, 433–437 (2012). https://doi.org/10.1038/nature11614

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