Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition
- Netherlands Institute for Neuroscience, Netherlands
- 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)
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ECoG_LFP_raw_Longterm_recording_dataDryad Digital Repository, doi:10.5061/dryad.pk0p2ngpk.
Article and author information
Author details
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.
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).
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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Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition
eLife 11:e73827.
https://doi.org/10.7554/eLife.73827
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