Myelination synchronizes cortical oscillations by consolidating parvalbumin-mediated phasic inhibition

Mohit Dubey, Maria Pascual-Garcia, Koke Helmes, Dennis D Wever, Mustafa S Hamada, Steven A Kushner, Maarten H P Kole

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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.

Originele taal-2Engels
Artikelnummere73827
TijdschrifteLife
Volume11
DOI's
StatusGepubliceerd - 10 jan. 2022

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