1. Computational and Systems Biology
  2. Neuroscience
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Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons

  1. Philipe RF Mendonça
  2. Mariana Vargas-Caballero
  3. Ferenc Erdélyi
  4. Gábor Szabó
  5. Ole Paulsen
  6. Hugh PC Robinson  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Southampton, United Kingdom
  3. Institute of Experimental Medicine, Hungary
Research Article
  • Cited 11
  • Views 1,802
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Cite this article as: eLife 2016;5:e16475 doi: 10.7554/eLife.16475

Abstract

Most cortical neurons fire regularly when excited by a constant stimulus. In contrast, irregular-spiking (IS) interneurons are remarkable for the intrinsic variability of their spike timing, which can synchronize amongst IS cells via specific gap junctions. Here, we have studied the biophysical mechanisms of this irregular spiking in mice, and how IS cells fire in the context of synchronous network oscillations. Using patch-clamp recordings, artificial dynamic conductance injection, pharmacological analysis and computational modelling, we show that spike time irregularity is generated by a nonlinear dynamical interaction of voltage-dependent sodium and fast-inactivating potassium channels just below spike threshold, amplifying channel noise. This active irregularity may help IS cells synchronize with each other at gamma range frequencies, while resisting synchronization to lower input frequencies.

Article and author information

Author details

  1. Philipe RF Mendonça

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Mariana Vargas-Caballero

    Institute for Life Sciences and Centre for Biological Sciences, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2326-4001
  3. Ferenc Erdélyi

    Division of Medical Gene Technology, Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Gábor Szabó

    Division of Medical Gene Technology, Institute of Experimental Medicine, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. Ole Paulsen

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2258-5455
  6. Hugh PC Robinson

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    hpcr@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5048-9954

Funding

Biotechnology and Biological Sciences Research Council

  • Ole Paulsen
  • Hugh PC Robinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

  • Philipe RF Mendonça

Cambridge Overseas Trust

  • Philipe RF Mendonça

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 and animal use were in accordance with the animal care guidelines of the UK Animals (Scientific Procedures) Act 1986 under Home Office project license PPL80/2440 and personal licenses held by the authors. Caution wastaken to minimize stress and the number of animals used in experiments.

Reviewing Editor

  1. Frances K Skinner, University Health Network, Canada

Publication history

  1. Received: March 29, 2016
  2. Accepted: August 17, 2016
  3. Accepted Manuscript published: August 18, 2016 (version 1)
  4. Version of Record published: September 20, 2016 (version 2)

Copyright

© 2016, Mendonça 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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