Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition

  1. Kevin M Collins  Is a corresponding author
  2. Addys Bode
  3. Robert W Fernandez
  4. Jessica E Tanis
  5. Jacob C Brewer
  6. Matthew S Creamer
  7. Michael R Koelle
  1. University of Miami, United States
  2. Yale University, United States

Abstract

Like many behaviors, Caenorhabditis elegans egg laying alternates between inactive and active states. To understand how the underlying neural circuit turns the behavior on and off, we optically recorded circuit activity in behaving animals while manipulating circuit function using mutations, optogenetics, and drugs. In the active state, the circuit shows rhythmic activity phased with the body bends of locomotion. The serotonergic HSN command neurons initiate the active state, but accumulation of unlaid eggs also promotes the active state independent of the HSNs. The cholinergic VC motor neurons slow locomotion during egg-laying muscle contraction and egg release. The uv1 neuroendocrine cells mechanically sense passage of eggs through the vulva and release tyramine to inhibit egg laying, in part via the LGC-55 tyramine-gated Cl- channel on the HSNs. Our results identify discrete signals that entrain or detach the circuit from the locomotion central pattern generator to produce active and inactive states.

Article and author information

Author details

  1. Kevin M Collins

    Department of Biology, University of Miami, Coral Gables, United States
    For correspondence
    kcollins@bio.miami.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9930-0924
  2. Addys Bode

    Department of Biology, University of Miami, Coral Gables, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Robert W Fernandez

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jessica E Tanis

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jacob C Brewer

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2780-2874
  6. Matthew S Creamer

    Interdepartmental Neuroscience Program, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael R Koelle

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9486-8481

Funding

American Heart Association (Postdoctoral Fellowship, POST4990016)

  • Kevin M Collins

National Institute of Neurological Disorders and Stroke (NS086932)

  • Kevin M Collins
  • Michael R Koelle

National Institute of Neurological Disorders and Stroke (NS036918)

  • Michael R Koelle

Yale Liver Center (DK34989)

  • Kevin M Collins

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

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: August 31, 2016
  2. Accepted: November 14, 2016
  3. Accepted Manuscript published: November 16, 2016 (version 1)
  4. Version of Record published: December 7, 2016 (version 2)

Copyright

© 2016, Collins 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

  • 5,683
    Page views
  • 641
    Downloads
  • 40
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, 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)

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

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

  1. Kevin M Collins
  2. Addys Bode
  3. Robert W Fernandez
  4. Jessica E Tanis
  5. Jacob C Brewer
  6. Matthew S Creamer
  7. Michael R Koelle
(2016)
Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition
eLife 5:e21126.
https://doi.org/10.7554/eLife.21126

Further reading

    1. Neuroscience
    David S Jacobs, Madeleine C Allen ... Bita Moghaddam
    Research Advance Updated

    Previously, we developed a novel model for anxiety during motivated behavior by training rats to perform a task where actions executed to obtain a reward were probabilistically punished and observed that after learning, neuronal activity in the ventral tegmental area (VTA) and dorsomedial prefrontal cortex (dmPFC) represent the relationship between action and punishment risk (Park and Moghaddam, 2017). Here, we used male and female rats to expand on the previous work by focusing on neural changes in the dmPFC and VTA that were associated with the learning of probabilistic punishment, and anxiolytic treatment with diazepam after learning. We find that adaptive neural responses of dmPFC and VTA during the learning of anxiogenic contingencies are independent from the punisher experience and occur primarily during the peri-action and reward period. Our results also identify peri-action ramping of VTA neural calcium activity, and VTA-dmPFC correlated activity, as potential markers for the anxiolytic properties of diazepam.

    1. Neuroscience
    Haiwei Zhang, Hongchen Li ... Ping Lv
    Research Article Updated

    Repressor element 1-silencing transcription factor (REST) is a transcriptional repressor that recognizes neuron-restrictive silencer elements in the mammalian genomes in a tissue- and cell-specific manner. The identity of REST target genes and molecular details of how REST regulates them are emerging. We performed conditional null deletion of Rest (cKO), mainly restricted to murine hair cells (HCs) and auditory neurons (aka spiral ganglion neurons [SGNs]). Null inactivation of full-length REST did not affect the development of normal HCs and SGNs but manifested as progressive hearing loss in adult mice. We found that the inactivation of REST resulted in an increased abundance of Kv7.4 channels at the transcript, protein, and functional levels. Specifically, we found that SGNs and HCs from Rest cKO mice displayed increased Kv7.4 expression and augmented Kv7 currents; SGN’s excitability was also significantly reduced. Administration of a compound with Kv7.4 channel activator activity, fasudil, recapitulated progressive hearing loss in mice. In contrast, inhibition of the Kv7 channels by XE991 rescued the auditory phenotype of Rest cKO mice. Previous studies identified some loss-of-function mutations within the Kv7.4-coding gene, Kcnq4, as a causative factor for progressive hearing loss in mice and humans. Thus, the findings reveal that a critical homeostatic Kv7.4 channel level is required for proper auditory functions.