Abstract

Large scale transitions between active (up) and silent (down) states during quiet wakefulness or NREM sleep regulate fundamental cortical functions and are known to involve both excitatory and inhibitory cells. However, if and how inhibition regulates these activity transitions is unclear. Using fluorescence-targeted electrophysiological recording and cell-specific optogenetic manipulation in both anesthetized and non-anesthetized mice, we found that two major classes of interneurons, the parvalbumin and the somatostatin positive cells, tightly control both up-to-down and down-to-up state transitions. Inhibitory regulation of state transition was found under both natural and optogenetically-evoked conditions, and was interneuron-type specific. Moreover, local manipulation of small ensembles of interneurons affected cortical populations millimetres away from the modulated region. Together, these results demonstrate that inhibition potently gates transitions between cortical activity states, and reveal the cellular mechanisms by which local inhibitory microcircuits regulate state transitions at the mesoscale.

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Author details

  1. Stefano Zucca

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Giulia D'Urso

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Valentina Pasquale

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4499-9536
  4. Dania Vecchia

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Giuseppe Pica

    Center of Neuroscience and Cognitive Systems, Italian Institute of Technology, Rovereto, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Serena Bovetti

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  7. Claudio Moretti

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Stefano Varani

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  9. Manuel Molano-Mazón

    Center of Neuroscience and Cognitive Systems, Italian Institute of Technology, Rovereto, Italy
    Competing interests
    The authors declare that no competing interests exist.
  10. Michela Chiappalone

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  11. Stefano Panzeri

    Center for Neuroscience and Cognitive Systems, Italian Institute of Technology, Rovereto, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1700-8909
  12. Tommaso Fellin

    Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy
    For correspondence
    tommaso.fellin@iit.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2718-7533

Funding

European Research Council (NEURO-PATTERNS)

  • Tommaso Fellin

National Institutes of Health (1U01NS090576-01)

  • Tommaso Fellin

Seventh Framework Programme (DESIRE)

  • Tommaso Fellin

MIUR FIRB (RBAP11X42L)

  • Tommaso Fellin

Flag-Era JTC Human Brain Project (SLOW-DYN)

  • Stefano Panzeri
  • Tommaso Fellin

H2020 MSCA IF 2015: Manuel Molano ETIC (699829)

  • Manuel Molano-Mazón

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

Ethics

Animal experimentation: Experimental procedures involving animals have been approved by the IIT Animal Welfare Body and by the Italian Ministry of Health (authorization # 34/2015-PR and 125/2012-B), in accordance with the National legislation (D.Lgs. 26/2014) and the European legislation (European Directive 2010/63/EU). All surgery was performed under urethane or isofluorane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

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

Publication history

  1. Received: February 21, 2017
  2. Accepted: May 15, 2017
  3. Accepted Manuscript published: May 16, 2017 (version 1)
  4. Version of Record published: May 25, 2017 (version 2)

Copyright

© 2017, Zucca 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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  1. Stefano Zucca
  2. Giulia D'Urso
  3. Valentina Pasquale
  4. Dania Vecchia
  5. Giuseppe Pica
  6. Serena Bovetti
  7. Claudio Moretti
  8. Stefano Varani
  9. Manuel Molano-Mazón
  10. Michela Chiappalone
  11. Stefano Panzeri
  12. Tommaso Fellin
(2017)
An inhibitory gate for state transition in cortex
eLife 6:e26177.
https://doi.org/10.7554/eLife.26177

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