1. Neuroscience
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Release-dependent feedback inhibition by a presynaptically localized ligand-gated anion channel

  1. Seika Takayanagi-Kiya
  2. Keming Zhou
  3. Yishi Jin  Is a corresponding author
  1. University of California, San Diego, United States
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Cite this article as: eLife 2016;5:e21734 doi: 10.7554/eLife.21734
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Abstract

Presynaptic ligand-gated ion channels (LGICs) have long been proposed to affect neurotransmitter release and to tune neural circuit activity. However, the understanding of their in vivo physiological action remains limited, partly due to the complexity in channel types and scarcity of genetic models. Here we report that C. elegans LGC-46, a member of the Cys-loop acetylcholine (ACh)-gated chloride (ACC) channel family, localizes to presynaptic terminals of cholinergic motor neurons and regulates synaptic vesicle (SV) release kinetics upon evoked release of acetylcholine. Loss of lgc-46 prolongs evoked release, without altering spontaneous activity. Conversely, a gain-of-function mutation of lgc-46 shortens evoked release to reduce synaptic transmission. This inhibition of presynaptic release requires the anion selectivity of LGC-46, and can ameliorate cholinergic over-excitation in a C. elegans model of excitation-inhibition imbalance. These data demonstrate a novel mechanism of presynaptic negative feedback in which an anion-selective LGIC acts as an auto-receptor to inhibit SV release.

Article and author information

Author details

  1. Seika Takayanagi-Kiya

    Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Keming Zhou

    Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yishi Jin

    Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    For correspondence
    yijin@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9371-9860

Funding

National Institutes of Health (R01, 035546)

  • Yishi Jin

Howard Hughes Medical Institute (Yishi Jin)

  • Yishi Jin

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: September 21, 2016
  2. Accepted: October 25, 2016
  3. Accepted Manuscript published: October 26, 2016 (version 1)
  4. Version of Record published: November 9, 2016 (version 2)

Copyright

© 2016, Takayanagi-Kiya 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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