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Layered reward signalling through octopamine and dopamine in Drosophila


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.


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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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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.

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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).

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