An hourglass circuit motif transforms a motor program via subcellularly localized muscle calcium signaling and contraction

  1. Steven R Sando  Is a corresponding author
  2. Nikhil Bhatla
  3. Eugene L Q Lee
  4. H Robert Horvitz  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. Miller Institute, Helen Wills Neuroscience Institute, University of California, Berkeley, United States

Abstract

Neural control of muscle function is fundamental to animal behavior. Many muscles can generate multiple distinct behaviors. Nonetheless, individual muscle cells are generally regarded as the smallest units of motor control. We report that muscle cells can alter behavior by contracting subcellularly. We previously discovered that noxious tastes reverse the net flow of particles through the C. elegans pharynx, a neuromuscular pump, resulting in spitting. We now show that spitting results from the subcellular contraction of the anterior region of the pm3 muscle cell. Subcellularly localized calcium increases accompany this contraction. Spitting is controlled by an 'hourglass' circuit motif: parallel neural pathways converge onto a single motor neuron that differentially controls multiple muscles and the critical subcellular muscle compartment. We conclude that subcellular muscle units enable modulatory motor control and propose that subcellular muscle contraction is a fundamental mechanism by which neurons can reshape behavior.

Data availability

All numerical data and analyses generated during this study are included in the manuscript and supporting files. Each figure and figure supplement is accompanied by a source data file that includes all numerical data used to generate that figure. This includes all excel files, all matlab data files and figures, all statistical analyses, and the .svg (scalable vector graphic) file used to generate each figure.All custom Matlab scripts used in data analysis and the sequences of all plasmids generated in this study are also included in separate source data files.In addition, all raw imaging data (i.e., confocal micrographs, calcium imaging videos, and all high-speed behavioral videos) are available for download on FigShare (doi: 10.6084/m9.figshare.c.5485554).

The following data sets were generated

Article and author information

Author details

  1. Steven R Sando

    Biology, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    srsando@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1101-9810
  2. Nikhil Bhatla

    Molecular and Cellular Biology, Miller Institute, Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eugene L Q Lee

    Biology, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4725-4959
  4. H Robert Horvitz

    Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    horvitz@mit.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9964-9613

Funding

National Institutes of Health (T32GM007287)

  • Steven R Sando

National Institutes of Health (GM024663)

  • Steven R Sando
  • Nikhil Bhatla
  • H Robert Horvitz

McGovern Institute (Friends of the McGovern Institute Fellowship)

  • Steven R Sando
  • Eugene L Q Lee

Lord Foundation (Lord Foundation Fellowship)

  • Steven R Sando

National Science Foundation (Graduate Research Fellowship)

  • Nikhil Bhatla

Agency for Science, Technology and Research (National Science Scholarship)

  • Eugene L Q Lee

Howard Hughes Medical Institute

  • H Robert Horvitz

Miller Institute (Miller Institute Research Fellowship)

  • Nikhil Bhatla

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

Reviewing Editor

  1. Manuel Zimmer, Research Institute of Molecular Pathology, Vienna Biocenter and University of Vienna, Austria

Publication history

  1. Received: May 26, 2020
  2. Accepted: June 26, 2021
  3. Accepted Manuscript published: July 2, 2021 (version 1)
  4. Version of Record published: August 3, 2021 (version 2)

Copyright

© 2021, Sando 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. Steven R Sando
  2. Nikhil Bhatla
  3. Eugene L Q Lee
  4. H Robert Horvitz
(2021)
An hourglass circuit motif transforms a motor program via subcellularly localized muscle calcium signaling and contraction
eLife 10:e59341.
https://doi.org/10.7554/eLife.59341
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