1. Neuroscience
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Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon

  1. Jessica E Messier
  2. Hongmei Chen
  3. Zhao-Lin Cai
  4. Mingshan Xue  Is a corresponding author
  1. Baylor College of Medicine, United States
Research Article
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Cite as: eLife 2018;7:e38506 doi: 10.7554/eLife.38506

Abstract

Light-gated chloride channels are emerging as promising optogenetic tools for inhibition of neural activity. However, their effects depend on the transmembrane chloride electrochemical gradient and may be complex due to the heterogeneity of this gradient in different developmental stages, neuronal types, and subcellular compartments. Here we characterized a light-gated chloride channel, GtACR2, in mouse cortical neurons. We found that GtACR2 activation inhibited the soma, but unexpectedly depolarized the presynaptic terminals resulting in neurotransmitter release. Other light-gated chloride channels had similar effects. Reducing the chloride concentrations in the axon and presynaptic terminals diminished the GtACR2-induced neurotransmitter release, indicating an excitatory effect of chloride channels in these compartments. A novel hybrid somatodendritic targeting motif reduced the GtACR2-induced neurotransmitter release while enhancing the somatic photocurrents. Our results highlight the necessity of precisely determining the effects of light-gated chloride channels under specific experimental conditions and provide a much-improved light-gated chloride channel for optogenetic inhibition.

Article and author information

Author details

  1. Jessica E Messier

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-5865-7043
  2. Hongmei Chen

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhao-Lin Cai

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-4034-2884
  4. Mingshan Xue

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    Mingshan.Xue@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-1463-8884

Funding

Whitehall Foundation (2015-05-54)

  • Mingshan Xue

Robert and Janice McNair Foundation (M.D./Ph.D. Student Scholarship)

  • Jessica E Messier

National Institutes of Health (R01NS100893)

  • Mingshan Xue

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All procedures to maintain and use mice were approved in the Animal Research Protocol AN-6544 by the Institutional Animal Care and Use Committee at Baylor College of Medicine.

Reviewing Editor

  1. Indira M Raman, Reviewing Editor, Northwestern University, United States

Publication history

  1. Received: May 19, 2018
  2. Accepted: August 8, 2018
  3. Accepted Manuscript published: August 9, 2018 (version 1)

Copyright

© 2018, Messier 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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