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A subset of dopamine neurons signals reward for odour memory in Drosophila

Nature volume 488, pages 512–516 (2012)Cite this article

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Abstract

Animals approach stimuli that predict a pleasant outcome1. After the paired presentation of an odour and a reward, Drosophila melanogaster can develop a conditioned approach towards that odour2,3. Despite recent advances in understanding the neural circuits for associative memory and appetitive motivation4, the cellular mechanisms for reward processing in the fly brain are unknown. Here we show that a group of dopamine neurons in the protocerebral anterior medial (PAM) cluster signals sugar reward by transient activation and inactivation of target neurons in intact behaving flies. These dopamine neurons are selectively required for the reinforcing property of, but not a reflexive response to, the sugar stimulus. In vivo calcium imaging revealed that these neurons are activated by sugar ingestion and the activation is increased on starvation. The output sites of the PAM neurons are mainly localized to the medial lobes of the mushroom bodies (MBs), where appetitive olfactory associative memory is formed5,6. We therefore propose that the PAM cluster neurons endow a positive predictive value to the odour in the MBs. Dopamine in insects is known to mediate aversive reinforcement signals5,7,8,9,10,11. Our results highlight the cellular specificity underlying the various roles of dopamine and the importance of spatially segregated local circuits within the MBs.

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Figure 1: Thermo-activation with DDC-GAL4 induces appetitive memory.
Figure 2: The PAM cluster neurons signal reward for olfactory memory.
Figure 3: The PAM neurons convey the reward signal to the MB.
Figure 4: The PAM neurons integrate reward and relevant signals.

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Acknowledgements

We thank L. Bräcker, M. Feind, C. Murphy, C. Schnaitmann and T. Templier for technical assistance and experiments that inspired this study; P. Garrity, the Kyoto Drosophila Genetic Resource Center and the Bloomington Stock Center for fly stocks; and Y.Y. Ma, Z. Q. Meng, R. Menzel, A. Thum, S. Waddell and the members of the Tanimoto laboratory for discussion and/or critical reading of the manuscript. C.L., Y.A., N.Y. and P.-Y.P. were sponsored by a Chinese–European doctoral training program from Max-Planck-Gesellschaft and the Chinese Academy of Sciences, the Deutscher Akademischer Austausch Dienst, the Alexander von Humboldt Foundation, and the Région Île-de-France, respectively. This work was supported by the Agence Nationale pour la Recherche (T.P.), the Howard Hughes Medical Institute (G.M.R.), Bernstein Focus Learning from the Bundesministerium für Bildung und Forschung and the Max-Planck-Gesellschaft (H.T.).

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Authors and Affiliations

  1. Max-Planck-Institut für Neurobiologie, Martinsried, 82152, Germany

    Chang Liu, Nobuhiro Yamagata, Yoshinori Aso, Anja B. Friedrich, Igor Siwanowicz & Hiromu Tanimoto

  2. Laboratory of Primate Cognitive Neuroscience, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650223, China,

    Chang Liu

  3. Graduate University of the Chinese Academy of Sciences, Beijing, 100049, China

    Chang Liu

  4. Genes and Dynamics of Memory Systems, Neurobiology Unit, Centre National de la Recherche Scientifique, École Supérieure de Physique et de Chimie Industrielles, 75005 Paris, France,

    Pierre-Yves Plaçais & Thomas Preat

  5. Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA,

    Barret D. Pfeiffer, Yoshinori Aso & Gerald M. Rubin

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  1. Chang Liu
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Contributions

C.L., N.Y., Y.A. and H.T. designed and C.L. and N.Y. performed all the behavioural experiments in this study. P.Y.P., T.P. and H.T. designed in vivo imaging experiments, and P.Y.P. and T.P. devised a new gustatory stimulation method. P.Y.P. performed imaging experiments and analysed the data. B.D.P. and G.M.R. designed and generated the new transgenic flies (GAL4, GAL80, LexA and LexAop2-dTrpA1 lines). Y.A. and H.T. identified R58E02 by using a database of GAL4 expression patterns created by G.M.R. and the Janelia Farm Fly Light Project Team. A.B.F. and I.S. performed immunohistochemistry, and C.L., A.B.F. and H.T. analysed the microscopic data. C.L. and H.T. made the figures and wrote the paper with the help of all the other authors.

Corresponding author

Correspondence to Hiromu Tanimoto.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-9 and full legends for Supplementary Movies 1-5. (PDF 2556 kb)

Supplementary Movie 1

This file contains a movie showing the expression pattern of R58E02-GAL4 in the brain. (AVI 5628 kb)

Supplementary Movie 2

This file contains a movie showing the expression pattern of DDC-GAL4 in the central brain. (AVI 4362 kb)

Supplementary Movie 3

This file contains a movie showing the expression pattern of DDC-GAL4 with R58E02-GAL80 in the central brain. (AVI 3834 kb)

Supplementary Movie 4

This file contains a movie showing differential labelling of NP5272-GAL4 and R58E02-LexA in the cell body region of the PAM cluster. (AVI 116 kb)

Supplementary Movie 5

This file contains a movie showing differential labelling of TH-GAL4 and R58E02-LexA in the MB. (AVI 3819 kb)

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Liu, C., Plaçais, PY., Yamagata, N. et al. A subset of dopamine neurons signals reward for odour memory in Drosophila. Nature 488, 512–516 (2012). https://doi.org/10.1038/nature11304

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