1. Neuroscience
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Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks

  1. Gertrudis Perea  Is a corresponding author
  2. Ricardo Gómez
  3. Sara Mederos
  4. Ana Covelo
  5. Jesús J Ballesteros
  6. Laura Schlosser
  7. Alicia Hernández-Vivanco
  8. Mario Martín-Fernández
  9. Ruth Quintana
  10. Abdelrahman Rayan
  11. Adolfo Díez
  12. Marco Fuenzalida
  13. Amit Agarwal
  14. Dwight E Bergles
  15. Bernhard Bettler
  16. Denise Manahan-Vaughan
  17. Eduardo D Martín
  18. Frank Kirchhoff
  19. Alfonso Araque  Is a corresponding author
  1. Instituto Cajal, Spain
  2. University of Minnesota, United States
  3. University of Castilla-La Mancha, Spain
  4. University of Saarland, Germany
  5. Ruhr University Bochum, Germany
  6. Universidad de Valparaíso, Chile
  7. Johns Hopkins School of Medicine, United States
  8. University of Basel, Switzerland
Research Article
  • Cited 54
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Cite this article as: eLife 2016;5:e20362 doi: 10.7554/eLife.20362

Abstract

Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

Article and author information

Author details

  1. Gertrudis Perea

    Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain
    For correspondence
    gperea@cajal.csic.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5924-9175
  2. Ricardo Gómez

    Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Sara Mederos

    Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Ana Covelo

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jesús J Ballesteros

    Albacete Science and Technology Park, Institute for Research in Neurological Disabilities, University of Castilla-La Mancha, Albacete, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Laura Schlosser

    Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Alicia Hernández-Vivanco

    Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Mario Martín-Fernández

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ruth Quintana

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Abdelrahman Rayan

    Department of Neurophysiology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Adolfo Díez

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Marco Fuenzalida

    Center of Neurobiology and Brain Plasticity, Universidad de Valparaíso, Valparaiso, Chile
    Competing interests
    The authors declare that no competing interests exist.
  13. Amit Agarwal

    Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7948-4498
  14. Dwight E Bergles

    Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Bernhard Bettler

    Department of Biomedicine, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  16. Denise Manahan-Vaughan

    Department of Neurophysiology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
  17. Eduardo D Martín

    Albacete Science and Technology Park, Institute for Research in Neurological Disabilities, University of Castilla-La Mancha, Albacete, Spain
    Competing interests
    The authors declare that no competing interests exist.
  18. Frank Kirchhoff

    Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  19. Alfonso Araque

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    For correspondence
    araque@umn.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

Ministerio de Economía y Competitividad

  • Gertrudis Perea
  • Ricardo Gómez

European Commission

  • Frank Kirchhoff
  • Alfonso Araque

Deutsche Forschungsgemeinschaft

  • Denise Manahan-Vaughan
  • Frank Kirchhoff

Human Frontier Science Program

  • Alfonso Araque

National Institute of Neurological Disorders and Stroke (NIH-NINDS (R01NS097312-01))

  • Alfonso Araque

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 the procedures for handling and sacrificing animals followed the European Commission guidelines for the welfare of experimental animals (2010/63/EU), US National Institutes of Health and the Institutional Animal Care and Use Committee at the University of Minnesota (USA). The use of astrocyte-specific GABBR1 knockout mice was approved by the Saarland state´s "Landesamt fÃ1/4r Gesundheit und Verbraucherschutz" in SaarbrÃ1/4cken/Germany (animal license number 72/2010).

Reviewing Editor

  1. Marlene Bartos, Albert-Ludwigs-Universität Freiburg, Germany

Publication history

  1. Received: August 5, 2016
  2. Accepted: December 23, 2016
  3. Accepted Manuscript published: December 24, 2016 (version 1)
  4. Version of Record published: January 12, 2017 (version 2)

Copyright

© 2016, Perea 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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