Prefrontal gamma oscillations and fear extinction learning require early postnatal interneuron-oligodendroglia communication

Abstract Emerging evidence links oligodendrocyte (OL) lineage cells and myelin to cognitive processes, yet the role of myelination in shaping neuronal networks critical for cognitive tasks remains unknown. We demonstrate in mice that early postnatal GABAergic signaling between interneurons and oligodendrocyte precursor cells (OPCs) is crucial for myelination of parvalbumin (PV) interneurons, which facilitates in vivo low-gamma oscillations in the medial prefrontal cortex (mPFC) and supports fear extinction learning. Disruption of this signaling results in PV interneuron dysmyelination, decreases low-gamma power, and impairs tone fear extinction. These deficits are specific to PV interneuron dysmyelination, as mPFC myelination, high-gamma oscillations and contextual fear extinction are not significantly altered. Increasing PV interneuron activity or enhancing myelination do not reverse the deficits, indicating the long-term consequences of these early myelination impairments. Our findings reveal the role of OPC GABAergic signaling in PV interneuron myelination and mPFC circuit maturation, with lasting impacts on gamma rhythms and cognition. Brief Summary Early postnatal interneuron-oligodendroglia communication may shape neuronal networks underlying cognition. Here, the authors show that disrupting this signaling in mice impairs interneuron myelination, gamma rhythms, and fear-related learning.