Botulinum neurotoxin accurately separates tonic vs phasic transmission and reveals heterosynaptic plasticity rules in Drosophila

  1. Yifu Han
  2. Chun Chien
  3. Pragya Goel
  4. Kaikai He
  5. Cristian Pinales
  6. Christopher Buser
  7. Dion K Dickman  Is a corresponding author
  1. University of Southern California, United States
  2. Oak Crest Institute of Science, United States

Abstract

In developing and mature nervous systems, diverse neuronal subtypes innervate common targets to establish, maintain, and modify neural circuit function. A major challenge towards understanding the structural and functional architecture of neural circuits is to separate these inputs and determine their intrinsic and heterosynaptic relationships. The Drosophila larval neuromuscular junction is a powerful model system to study these questions, where two glutamatergic motor neurons, the strong phasic-like <strong>Is</strong> and weak tonic-like <strong>Ib</strong>, co-innervate individual muscle targets to coordinate locomotor behavior. However, complete neurotransmission from each input has never been electrophysiologically separated. We have employed a botulinum neurotoxin, BoNT-C, that eliminates both spontaneous and evoked neurotransmission without perturbing synaptic growth or structure, enabling the first approach that accurately isolates input-specific neurotransmission. Selective expression of BoNT-C in Is or Ib motor neurons disambiguates the functional properties of each input. Importantly, the blended values of Is+Ib neurotransmission can be fully recapitulated by isolated physiology from each input. Finally, selective silencing by BoNT-C does not induce heterosynaptic structural or functional plasticity at the convergent input. Thus, BoNT-C establishes the first approach to accurately separate neurotransmission between tonic vs phasic neurons and defines heterosynaptic plasticity rules in a powerful model glutamatergic circuit.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. In particular, full details of the data are included in Supplemental files 1 and 2.

Article and author information

Author details

  1. Yifu Han

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1201-654X
  2. Chun Chien

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    No competing interests declared.
  3. Pragya Goel

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    No competing interests declared.
  4. Kaikai He

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    No competing interests declared.
  5. Cristian Pinales

    Oak Crest Institute of Science, Monrovia, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0826-5308
  6. Christopher Buser

    Oak Crest Institute of Science, Monrovia, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4379-3878
  7. Dion K Dickman

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    For correspondence
    dickman@usc.edu
    Competing interests
    Dion K Dickman, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1884-284X

Funding

National Institutes of Health (NS091546)

  • Dion K Dickman

National Institutes of Health (NS111414)

  • Dion K Dickman

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

Reviewing Editor

  1. Chris Q Doe, Howard Hughes Medical Institute, University of Oregon, United States

Publication history

  1. Received: February 16, 2022
  2. Preprint posted: February 17, 2022 (view preprint)
  3. Accepted: August 20, 2022
  4. Accepted Manuscript published: August 22, 2022 (version 1)
  5. Version of Record published: September 2, 2022 (version 2)

Copyright

© 2022, Han 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. Yifu Han
  2. Chun Chien
  3. Pragya Goel
  4. Kaikai He
  5. Cristian Pinales
  6. Christopher Buser
  7. Dion K Dickman
(2022)
Botulinum neurotoxin accurately separates tonic vs phasic transmission and reveals heterosynaptic plasticity rules in Drosophila
eLife 11:e77924.
https://doi.org/10.7554/eLife.77924

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