Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition

  1. Mohit Dubey
  2. Maria Pascual-Garcia
  3. Koke Helmes
  4. Dennis D Wever
  5. Mustafa S Hamada
  6. Steven A Kushner
  7. Maarten H P Kole  Is a corresponding author
  1. Netherlands Institute for Neuroscience, Netherlands
  2. Erasmus MC University Medical Center, Netherlands

Abstract

Parvalbumin-positive (PV+) γ-aminobutyric acid (GABA) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations but the significance of PV+ axon myelination to the temporal features of inhibition remains elusive. Here using toxic and genetic mouse models of demyelination and dysmyelination, respectively, we find that loss of compact myelin reduces PV+ interneuron presynaptic terminals, increases failures and the weak phasic inhibition of pyramidal neurons abolishes optogenetically driven gamma oscillations in vivo. Strikingly, during behaviors of quiet wakefulness selectively theta rhythms are amplified and accompanied by highly synchronized interictal epileptic discharges. In support of a causal role of impaired PV-mediated inhibition, optogenetic activation of myelin-deficient PV+ interneurons attenuated the power of slow theta rhythms and limited interictal spike occurrence. Thus, myelination of PV axons is required to consolidate fast inhibition of pyramidal neurons and enable behavioral state-dependent modulation of local circuit synchronization.

Data availability

Raw data for Figure 1d is accessible via Dryad (doi:10.5061/dryad.pk0p2ngpk)

The following data sets were generated
    1. Dubey M
    (2021) ECoG_LFP_raw_Longterm_recording_data
    Dryad Digital Repository, doi:10.5061/dryad.pk0p2ngpk.

Article and author information

Author details

  1. Mohit Dubey

    Department of Axonal Signaling, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9770-0633
  2. Maria Pascual-Garcia

    Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Koke Helmes

    Department of Axonal Signaling, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Dennis D Wever

    Department of Axonal Signaling, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Mustafa S Hamada

    Department of Axonal Signaling, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2232-6146
  6. Steven A Kushner

    Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9777-3338
  7. Maarten H P Kole

    Department of Axonal Signaling, Netherlands Institute for Neuroscience, Amsterdam, Netherlands
    For correspondence
    m.kole@nin.knaw.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3883-5682

Funding

National Multiple Sclerosis Society (RG-1602-07777)

  • Maarten H P Kole

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Vici 865.17.003)

  • Maarten H P Kole

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (013.18.002)

  • Steven A Kushner

ERA-NET (JTC2018-024)

  • Steven A Kushner

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

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Ethics

Animal experimentation: All animal experiments were done in compliance with the European Communities Council Directive 2010/63/EU effective from 1 January 2013. The experimental design and ethics were evaluated and approved by the national committee of animal experiments (CCD, application number AVD 80100 2017 2426). The specific experimental protocols involving animals were designed to minimize suffering and approved and monitored by the animal welfare body (IvD, protocol numbers; NIN17.21.04, NIN18.21.02, NIN18.21.05, NIN19.21.04 and, NIN20.21.02) of the Royal Netherlands Academy of Arts and Science (KNAW).

Version history

  1. Preprint posted: September 7, 2021 (view preprint)
  2. Received: September 14, 2021
  3. Accepted: December 28, 2021
  4. Accepted Manuscript published: January 10, 2022 (version 1)
  5. Version of Record published: February 17, 2022 (version 2)

Copyright

© 2022, Dubey 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. Mohit Dubey
  2. Maria Pascual-Garcia
  3. Koke Helmes
  4. Dennis D Wever
  5. Mustafa S Hamada
  6. Steven A Kushner
  7. Maarten H P Kole
(2022)
Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition
eLife 11:e73827.
https://doi.org/10.7554/eLife.73827

Share this article

https://doi.org/10.7554/eLife.73827

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