Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments

  1. Aaron Stahl
  2. Nathaniel C Noyes
  3. Tamara Boto
  4. Valentina Botero
  5. Connor N Broyles
  6. Miao Jing
  7. Jianzhi Zeng
  8. Lanikea B King
  9. Yulong Li
  10. Ronald L Davis
  11. Seth M Tomchik  Is a corresponding author
  1. Scripps Research Institute, United States
  2. Peking University, China
  3. Peiking University, China

Abstract

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor (IP3R), which maintained responsivity to odors upon repeated presentations, preventing adaptation. Downstream from the mushroom body, a set of MBONs that receive their input from the g3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which reward learning influences decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.

Data availability

Raw data have been deposited to Dryad under doi: 10.5061/dryad.dfn2z353h

The following data sets were generated

Article and author information

Author details

  1. Aaron Stahl

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3170-1101
  2. Nathaniel C Noyes

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Tamara Boto

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9974-3714
  4. Valentina Botero

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9744-3929
  5. Connor N Broyles

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2930-7343
  6. Miao Jing

    Chinese Institute for Brain Research, Peking University, Peking, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Jianzhi Zeng

    Peking-Tsinghua Center for Life Sciences, Peiking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5380-6281
  8. Lanikea B King

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Yulong Li

    State Key Laboratory of Membrane Biology, Peiking University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Ronald L Davis

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Seth M Tomchik

    Department of Neuroscience, Scripps Research Institute, Jupiter, United States
    For correspondence
    STomchik@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5686-0833

Funding

National Institutes of Health (R01NS097237)

  • Seth M Tomchik

National Institutes of Health (NS103558)

  • Yulong Li

National Institutes of Health (R01NS114403)

  • Seth M Tomchik

National Institutes of Health (R00MH092294)

  • Seth M Tomchik

Whitehall Foundation (2014-12-31)

  • Seth M Tomchik

National Institutes of Health (R35NS097224)

  • Ronald L Davis

Beijing Municipal Science & Technology Commission (Z181100001318002)

  • Yulong Li

Beijing Brain Initiative of Beijing Municipal Science & Technology Commission (Z181100001518004)

  • Yulong Li

Guangdong Grant Key Technologies for Treatment of Brain Disorders"" (2018B030332001)

  • Yulong Li

General Program of National Natural Science Foundation of China Projects (31671118,31871087,31925017)

  • Yulong Li

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

Version history

  1. Preprint posted: June 10, 2021 (view preprint)
  2. Received: December 30, 2021
  3. Accepted: March 11, 2022
  4. Accepted Manuscript published: March 14, 2022 (version 1)
  5. Version of Record published: March 25, 2022 (version 2)

Copyright

© 2022, Stahl 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. Aaron Stahl
  2. Nathaniel C Noyes
  3. Tamara Boto
  4. Valentina Botero
  5. Connor N Broyles
  6. Miao Jing
  7. Jianzhi Zeng
  8. Lanikea B King
  9. Yulong Li
  10. Ronald L Davis
  11. Seth M Tomchik
(2022)
Associative learning drives longitudinally-graded presynaptic plasticity of neurotransmitter release along axonal compartments
eLife 11:e76712.
https://doi.org/10.7554/eLife.76712

Share this article

https://doi.org/10.7554/eLife.76712

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