Letter | Published:

Re-evaluation of learned information in Drosophila

Nature volume 544, pages 240244 (13 April 2017) | Download Citation

Abstract

Animals constantly assess the reliability of learned information to optimize their behaviour. On retrieval, consolidated long-term memory can be neutralized by extinction if the learned prediction was inaccurate1. Alternatively, retrieved memory can be maintained, following a period of reconsolidation during which it is labile2. Although extinction and reconsolidation provide opportunities to alleviate problematic human memories3,4,5, we lack a detailed mechanistic understanding of memory updating. Here we identify neural operations underpinning the re-evaluation of memory in Drosophila. Reactivation of reward-reinforced olfactory memory can lead to either extinction or reconsolidation, depending on prediction accuracy. Each process recruits activity in specific parts of the mushroom body output network and distinct subsets of reinforcing dopaminergic neurons. Memory extinction requires output neurons with dendrites in the α and α′ lobes of the mushroom body, which drive negatively reinforcing dopaminergic neurons that innervate neighbouring zones. The aversive valence of these new extinction memories neutralizes previously learned odour preference. Memory reconsolidation requires the γ2α′1 mushroom body output neurons. This pathway recruits negatively reinforcing dopaminergic neurons innervating the same compartment and re-engages positively reinforcing dopaminergic neurons to reconsolidate the original reward memory. These data establish that recurrent and hierarchical connectivity between mushroom body output neurons and dopaminergic neurons enables memory re-evaluation driven by reward-prediction error.

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Acknowledgements

We thank G. Rubin, FlyLight, Bloomington Stock Center and D. J. Anderson for flies. We are grateful to members of the Waddell group and G. Wright for discussion and comments on the manuscript. J.F. was supported by the Deutsche Forschungsgemeinschaft (FE 1563/1-1), S.L. an EMBO Long-Term Fellowship and O.B the Medical Research Council, University College War Memorial Studentship and a Goodger and Schorstein Scholarship. S.W. is funded by a Wellcome Trust Principal Research Fellowship in the Basic Biomedical Sciences, Gatsby Charitable Foundation, Oxford Martin School and Bettencourt–Schueller Foundation.

Author information

Author notes

    • Suewei Lin

    Present address: Institute of Molecular Biology, Academica Sinica, Taipei 115, Taiwan.

Affiliations

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

    • Johannes Felsenberg
    • , Oliver Barnstedt
    • , Paola Cognigni
    • , Suewei Lin
    •  & Scott Waddell

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Contributions

J.F. and S.W. conceived the project and designed all experiments. S.L. performed initial extinction experiments. J.F. performed and analysed all behavioural experiments with help from P.C. O.B. performed imaging experiments assisted by J.F. Live imaging data were analysed by O.B. and P.C. The manuscript was written by S.W. and J.F. with comments from P.C. and O.B.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Scott Waddell.

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Extended data

Supplementary information

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  1. 1.

    Supplementary Table 1

    This file contains details of sample numbers and statistics for Figures 1-4.

  2. 2.

    Supplementary Table 2

    This file contains details of sample numbers and statistics for Extended Data Figures 2-5.

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DOI

https://doi.org/10.1038/nature21716

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