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Differential conditioning produces merged long-term memory in Drosophila

  1. Bohan Zhao
  2. JIameng Sun
  3. Qian Li
  4. Yi Zhong  Is a corresponding author
  1. Tsinghua University, China
Research Article
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Cite this article as: eLife 2021;10:e66499 doi: 10.7554/eLife.66499


Multiple spaced trials of aversive differential conditioning can produce two independent long-term memories (LTMs) of opposite valence. One is an aversive memory for avoiding the conditioned stimulus (CS+), and the other is a safety memory for approaching the non-conditioned stimulus (CS-). Here, we show that a single trial of aversive differential conditioning yields one merged LTM (mLTM) for avoiding both CS+ and CS-. Such mLTM can be detected after sequential exposures to the shock-paired CS+ and unpaired CS-, and be retrieved by either CS+ or CS-. The formation of mLTM relies on triggering aversive-reinforcing dopaminergic neurons and subsequent new protein synthesis. Expressing mLTM involves αβ Kenyon cells and corresponding approach-directing mushroom body output neurons (MBONs), in which similar-amplitude long-term depression of responses to CS+ and CS- seems to signal the mLTM. Our results suggest that animals can develop distinct strategies for occasional and repeated threatening experiences.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Bohan Zhao

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. JIameng Sun

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Qian Li

    School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yi Zhong

    School of Life Sciences, Tsinghua University, Beijing, China
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7927-5976


National Science Foundation of China (31970955)

  • Qian Li

Tsinghua-Peking Center for Life Sciences

  • Yi Zhong

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: January 13, 2021
  2. Accepted: July 18, 2021
  3. Accepted Manuscript published: July 19, 2021 (version 1)


© 2021, Zhao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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