1. Neuroscience
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Spatiotemporal constraints on optogenetic inactivation in cortical circuits

  1. Nuo Li  Is a corresponding author
  2. Susu Chen
  3. Zengcai V Guo
  4. Han Chen
  5. Yan Huo
  6. Hidehiko K Inagaki
  7. Guang Chen
  8. Courtney Davis
  9. David Hansel
  10. Caiying Guo
  11. Karel Svoboda  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. Janelia Research Campus, Howard Hughes Medical Institute, United States
  3. Tsinghua University, China
  4. CNRS-UMR8119, France
Research Article
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Cite this article as: eLife 2019;8:e48622 doi: 10.7554/eLife.48622

Abstract

Optogenetics allows manipulations of genetically and spatially defined neuronal populations with excellent temporal control. However, neurons are coupled with other neurons over multiple length scales, and the effects of localized manipulations thus spread beyond the targeted neurons. We benchmarked several optogenetic methods to inactivate small regions of neocortex. Optogenetic excitation of GABAergic neurons produced more effective inactivation than light-gated ion pumps. Transgenic mice expressing the light-dependent chloride channel GtACR1 produced the most potent inactivation. Generally, inactivation spread substantially beyond the photostimulation light, caused by strong coupling between cortical neurons. Over some range of light intensity, optogenetic excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks ('paradoxical effect'). The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, limiting temporal resolution. Our data offer guidance for the design of in vivo optogenetics experiments.

Article and author information

Author details

  1. Nuo Li

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    nuol@bcm.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6613-5018
  2. Susu Chen

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  3. Zengcai V Guo

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  4. Han Chen

    School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    No competing interests declared.
  5. Yan Huo

    School of Medicine, Tsinghua University, Beijing, China
    Competing interests
    No competing interests declared.
  6. Hidehiko K Inagaki

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  7. Guang Chen

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  8. Courtney Davis

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    No competing interests declared.
  9. David Hansel

    Center of Neurophysics, Physiology and Pathologies, CNRS-UMR8119, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1352-6592
  10. Caiying Guo

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    No competing interests declared.
  11. Karel Svoboda

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    svobodak@janelia.hhmi.org
    Competing interests
    Karel Svoboda, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6670-7362

Funding

Howard Hughes Medical Institute

  • Karel Svoboda

Pew Charitable Trusts

  • Nuo Li

Simons Foundation

  • Nuo Li
  • Karel Svoboda

Helen Hay Whitney Foundation

  • Nuo Li
  • Hidehiko K Inagaki

Wellcome

  • Susu Chen

Robert and Janice McNair Foundation

  • Nuo Li

Whitehall Foundation

  • Nuo Li

Alfred P. Sloan Foundation

  • Nuo Li

Kinship Foundation

  • Nuo Li

National Institutes of Health (NS104781)

  • Nuo Li

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

Ethics

Animal experimentation: All procedures were in accordance with protocols approved by the Institutional Animal Care and Use Committees at Baylor College of Medicine (protocol AN7012), Janelia Research Campus (protocol 14-115).

Reviewing Editor

  1. John Huguenard, Stanford University School of Medicine, United States

Publication history

  1. Received: May 21, 2019
  2. Accepted: November 16, 2019
  3. Accepted Manuscript published: November 18, 2019 (version 1)
  4. Version of Record published: December 4, 2019 (version 2)

Copyright

© 2019, Li 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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