A growing body of work suggests a link between oligodendrocyte-lineage cells, myelin, and cognitive processes. Oligodendrocytes are glial cells of the central nervous system that produce myelin, the lipid sheath that surrounds axons, speeds up the propagation of nerve impulses and provides metabolic support. However, how myelination shapes the neuronal networks underlying cognitive tasks remained largely unknown. Cognitive functions rely on the coordination of excitatory and inhibitory neuronal networks, and in particular on gamma oscillations, whose rapid synchronization of excitatory activity is largely modulated by parvalbumin (PV) interneurons. The contribution of glial cells to this orchestration remained little explored.
In mice, the authors investigated the role of early GABAergic signaling, during the postnatal period, between interneurons and oligodendrocyte precursor cells (OPCs). They establish that this communication is critical for the myelination of parvalbumin interneurons. This myelination, in turn, promotes in vivo low-frequency gamma oscillations in the medial prefrontal cortex and supports fear extinction learning. The analyses combined electrophysiological patch-clamp approaches, immunostaining to quantify cell densities and internode lengths along PV interneuron axons, and behavioral tests, with all quantifications performed blinded to the experimental conditions.
Disruption of this signaling leads to dysmyelination of parvalbumin interneurons, a decrease in the power of low-frequency gamma oscillations, and impaired extinction of auditory cued fear. These deficits are specific to PV interneuron dysmyelination: overall myelination of the medial prefrontal cortex, high-frequency gamma oscillations, and contextual fear extinction are not significantly altered. Notably, neither enhancing parvalbumin interneuron activity nor boosting myelination is able to correct these deficits, underscoring the lasting nature of the consequences of these early myelination impairments.
This work thus highlights the role of GABAergic signaling from oligodendrocyte precursor cells in the myelination of parvalbumin interneurons and in the maturation of medial prefrontal cortex circuits. It reveals that an early developmental window persistently conditions gamma rhythms and certain cognitive functions, establishing an interneuron–oligodendroglia dialogue as a key element in the assembly of these networks.