Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila

  1. Daichi Yamada
  2. Daniel Bushey
  3. Feng Li
  4. Karen L Hibbard
  5. Megan Sammons
  6. Jan Funke
  7. Ashok Litwin-Kumar
  8. Toshihide Hige  Is a corresponding author
  9. Yoshinori Aso  Is a corresponding author
  1. University of North Carolina at Chapel Hill, United States
  2. Janelia Research Campus, United States
  3. Columbia University, United States

Abstract

Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective 'teacher' by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the 'student' compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.

Data availability

The confocal images of expression patterns are available online (http://www.janelia.org/split-gal4). The source data for each figure are included in the manuscript.

Article and author information

Author details

  1. Daichi Yamada

    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Bushey

    Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9258-6579
  3. Feng Li

    Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6658-9175
  4. Karen L Hibbard

    Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2001-6099
  5. Megan Sammons

    Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4516-5928
  6. Jan Funke

    Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4388-7783
  7. Ashok Litwin-Kumar

    Department of Neuroscience, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2422-6576
  8. Toshihide Hige

    Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States
    For correspondence
    hige@email.unc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0007-3192
  9. Yoshinori Aso

    Janelia Research Campus, Ashburn, United States
    For correspondence
    asoy@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2939-1688

Funding

NIH (R01DC018874)

  • Toshihide Hige

NSF (DBI-1707398)

  • Ashok Litwin-Kumar

Toyobo Biotechnology Foundation Postdoctoral Fellowship

  • Daichi Yamada

Japan Society for the Promotion of Science Overseas Research Fellowship

  • Daichi Yamada

HHMI

  • Daniel Bushey
  • Feng Li
  • Karen L Hibbard
  • Megan Sammons
  • Jan Funke
  • Yoshinori Aso

NSF (2034783)

  • Toshihide Hige

BSF (2019026)

  • Toshihide Hige

UNC Junior Faculty Development Award

  • Toshihide Hige

Burroughs Wellcome Foundation

  • Ashok Litwin-Kumar

Gatsby Charitable Foundation

  • Ashok Litwin-Kumar

McKnight Endowment Fund

  • Ashok Litwin-Kumar

Simons Collaboration on the Global Brain

  • Ashok Litwin-Kumar
  • Yoshinori Aso

NIH (R01EB029858)

  • Ashok Litwin-Kumar

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

Reviewing Editor

  1. Ilona C Grunwald Kadow, University of Bonn, Germany

Publication history

  1. Received: March 28, 2022
  2. Accepted: January 23, 2023
  3. Accepted Manuscript published: January 24, 2023 (version 1)

Copyright

© 2023, Yamada 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.

Metrics

  • 250
    Page views
  • 82
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Daichi Yamada
  2. Daniel Bushey
  3. Feng Li
  4. Karen L Hibbard
  5. Megan Sammons
  6. Jan Funke
  7. Ashok Litwin-Kumar
  8. Toshihide Hige
  9. Yoshinori Aso
(2023)
Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila
eLife 12:e79042.
https://doi.org/10.7554/eLife.79042