1. Neuroscience
Download icon

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
Research Article
  • Cited 8
  • Views 2,730
  • Annotations
Cite this article as: eLife 2019;8:e49257 doi: 10.7554/eLife.49257

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.

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)

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.

Metrics

  • 2,730
    Page views
  • 617
    Downloads
  • 8
    Citations

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

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)

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

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

  1. Further reading

Further reading

    1. Neuroscience
    Gabriela Manzano Nieves et al.
    Research Article Updated

    Early life adversity (ELA) is associated with increased risk for stress-related disorders later in life. The link between ELA and risk for psychopathology is well established but the developmental mechanisms remain unclear. Using a mouse model of resource insecurity, limited bedding (LB), we tested the effects of LB on the development of fear learning and neuronal structures involved in emotional regulation, the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA). LB delayed the ability of peri-weanling (21 days old) mice to express, but not form, an auditory conditioned fear memory. LB accelerated the developmental emergence of parvalbumin (PV)-positive cells in the BLA and increased anatomical connections between PL and BLA. Fear expression in LB mice was rescued through optogenetic inactivation of PV-positive cells in the BLA. The current results provide a model of transiently blunted emotional reactivity in early development, with latent fear-associated memories emerging later in adolescence.

    1. Neuroscience
    Víctor J López-Madrona et al.
    Research Article Updated

    Hippocampal firing is organized in theta sequences controlled by internal memory processes and by external sensory cues, but how these computations are coordinated is not fully understood. Although theta activity is commonly studied as a unique coherent oscillation, it is the result of complex interactions between different rhythm generators. Here, by separating hippocampal theta activity in three different current generators, we found epochs with variable theta frequency and phase coupling, suggesting flexible interactions between theta generators. We found that epochs of highly synchronized theta rhythmicity preferentially occurred during behavioral tasks requiring coordination between internal memory representations and incoming sensory information. In addition, we found that gamma oscillations were associated with specific theta generators and the strength of theta-gamma coupling predicted the synchronization between theta generators. We propose a mechanism for segregating or integrating hippocampal computations based on the flexible coordination of different theta frameworks to accommodate the cognitive needs.