1. Neuroscience

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
https://doi.org/10.7554/eLife.79042
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Cite this article
  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
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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.

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.

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  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

Share this article

https://doi.org/10.7554/eLife.79042

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Further reading

    1. Neuroscience

    Neural circuit mechanisms for transforming learned olfactory valences into wind-oriented movement

    Yoshinori Aso, Daichi Yamada ... Toshihide Hige
    Research Article Updated

    How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in Drosophila, multiple compartments of the mushroom body act in parallel to assign a valence to a stimulus. Here, we show that appetitive memories stored in different compartments induce different levels of upwind locomotion. Using a photoactivation screen of a new collection of split-GAL4 drivers and EM connectomics, we identified a cluster of neurons postsynaptic to the mushroom body output neurons (MBONs) that can trigger robust upwind steering. These UpWind Neurons (UpWiNs) integrate inhibitory and excitatory synaptic inputs from MBONs of appetitive and aversive memory compartments, respectively. After formation of appetitive memory, UpWiNs acquire enhanced response to reward-predicting odors as the response of the inhibitory presynaptic MBON undergoes depression. Blocking UpWiNs impaired appetitive memory and reduced upwind locomotion during retrieval. Photoactivation of UpWiNs also increased the chance of returning to a location where activation was terminated, suggesting an additional role in olfactory navigation. Thus, our results provide insight into how learned abstract valences are gradually transformed into concrete memory-driven actions through divergent and convergent networks, a neuronal architecture that is commonly found in the vertebrate and invertebrate brains.