1. Neuroscience
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Inhibitory peptidergic modulation of C. elegans serotonin neurons is gated by T-type calcium channels

  1. Kara E Zang
  2. Elver Ho
  3. Niels Ringstad  Is a corresponding author
  1. NYU Langone School of Medicine, United States
Research Article
  • Cited 5
  • Views 1,487
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Cite this article as: eLife 2017;6:e22771 doi: 10.7554/eLife.22771

Abstract

Serotonin is an evolutionarily ancient molecule that functions in generating and modulating many behavioral states. Although much is known about how serotonin acts on its cellular targets, how serotonin release is regulated in vivo remains poorly understood. In the nematode C. elegans, serotonin neurons that drive female reproductive behavior are directly modulated by inhibitory neuropeptides. Here, we report the isolation of mutants in which inhibitory neuropeptides fail to properly modulate serotonin neurons and the behavior they mediate. The corresponding mutations affect the T-type calcium channel CCA-1 and symmetrically re-tune its voltage-dependencies of activation and inactivation towards more hyperpolarized potentials. This shift in voltage dependency strongly and specifically bypasses the behavioral and cell physiological effects of peptidergic inhibition on serotonin neurons. Our results indicate that T-type calcium channels are critical regulators of a C. elegans serotonergic circuit and demonstrate a mechanism in which T-type channels functionally gate inhibitory modulation in vivo.

Article and author information

Author details

  1. Kara E Zang

    Skirball Institute for Biomolecular Medicine, NYU Langone School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Elver Ho

    Skirball Institute for Biomolecular Medicine, NYU Langone School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Niels Ringstad

    Skirball Institute for Biomolecular Medicine, NYU Langone School of Medicine, New York, United States
    For correspondence
    Niels.Ringstad@med.nyu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8679-2269

Funding

National Institute of General Medical Sciences (R01-098320)

  • Niels Ringstad

National Institute of General Medical Sciences (R01-113182)

  • Niels Ringstad

National Institute of Neurological Disorders and Stroke (F31NS089232)

  • Kara E Zang

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

Ethics

Animal experimentation: Animal subjects (Xenopus laevis frogs) were used in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to the approved institutional animal care and use committee (IACUC) protocol #131102-03.

Reviewing Editor

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

Publication history

  1. Received: October 28, 2016
  2. Accepted: February 6, 2017
  3. Accepted Manuscript published: February 6, 2017 (version 1)
  4. Version of Record published: February 28, 2017 (version 2)

Copyright

© 2017, Zang 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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