Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics

  1. Yoshinori Aso  Is a corresponding author
  2. Robert P Ray
  3. Xi Long
  4. Daniel Bushey
  5. Karol Cichewicz
  6. Teri-TB Ngo
  7. Brandi Sharp
  8. Christina Christoforou
  9. Amy Hu
  10. Andrew L Lemire
  11. Paul Tillberg
  12. Jay Hirsh
  13. Ashok Litwin-Kumar
  14. Gerald M Rubin  Is a corresponding author
  1. Janelia Research Campus, Howard Hughes Medical Institute, United States
  2. University of Virginia, United States
  3. Columbia University, United States

Abstract

Animals employ diverse learning rules and synaptic plasticity dynamics to record temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso & Rubin 2016). Here we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO's effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.

Data availability

Complete transcript data were deposited to NCBI Gene Expression Omnibus (accession number GSE139889).

The following data sets were generated

Article and author information

Author details

  1. Yoshinori Aso

    Janelia Research Campus, Howard Hughes Medical Institute, 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
  2. Robert P Ray

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xi Long

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0268-8641
  4. Daniel Bushey

    Janelia Research Campus, Howard Hughes Medical Institute, 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
  5. Karol Cichewicz

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Teri-TB Ngo

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Brandi Sharp

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christina Christoforou

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Amy Hu

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Andrew L Lemire

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Paul Tillberg

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Jay Hirsh

    Department of Biology, University of Virginia, Charlottesville, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. 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
  14. Gerald M Rubin

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    rubing@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8762-8703

Funding

Howard Hughes Medical Institute

  • Yoshinori Aso
  • Robert P Ray
  • Xi Long
  • Daniel Bushey
  • Teri-TB Ngo
  • Brandi Sharp
  • Christina Christoforou
  • Amy Hu
  • Andrew L Lemire
  • Paul Tillberg
  • Gerald M Rubin

National Institutes of Health (R01 GM84128)

  • Karol Cichewicz
  • Jay Hirsh

Simons Foundation (Global Brain)

  • Yoshinori Aso
  • Ashok Litwin-Kumar
  • Gerald M Rubin

Burroughs Wellcome Foundation

  • Ashok Litwin-Kumar

Gatsby Charitable Foundation

  • Ashok Litwin-Kumar

National Science Foundation (DBI-1707398)

  • 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. Mani Ramaswami, Trinity College Dublin, Ireland

Publication history

  1. Received: June 12, 2019
  2. Accepted: November 13, 2019
  3. Accepted Manuscript published: November 14, 2019 (version 1)
  4. Version of Record published: January 8, 2020 (version 2)
  5. Version of Record updated: October 22, 2020 (version 3)

Copyright

© 2019, Aso 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. Yoshinori Aso
  2. Robert P Ray
  3. Xi Long
  4. Daniel Bushey
  5. Karol Cichewicz
  6. Teri-TB Ngo
  7. Brandi Sharp
  8. Christina Christoforou
  9. Amy Hu
  10. Andrew L Lemire
  11. Paul Tillberg
  12. Jay Hirsh
  13. Ashok Litwin-Kumar
  14. Gerald M Rubin
(2019)
Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics
eLife 8:e49257.
https://doi.org/10.7554/eLife.49257
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