Oligodendrocyte-specificfusdepletion preserves CA1 single-unit fidelity and stabilizes network dynamics during...

Objective.Loss of oligodendrocytes (OLs) and myelin impairs neuronal firing and network stability, whereas enhancing oligodendrogenesis with clemastine improves electrophysiological stability in cortex and, to a lesser extent, hippocampus. Conditional depletion ofFusin OLs (Fus^OLcKO) drives developmentally regulated increases in myelin thickness via enhanced cholesterol biosynthesis. Here, we investigated whetherFus-depleted OLs differentially affected long-term extracellular recordings across cortical layers and hippocampal CA1.Approach.We performed chronic electrophysiological recordings in visual cortex and CA1 ofFus^OLcKO mice and littermate controls over 16 weeks, combined with endpoint histology.Main results.InFus^OLcKO mice, visually-evoked single-unit detectability and firing rate in CA1 increased relative to wild-type littermates, whereas cortical recordings showed no improvement. At the population level,Fus^OLcKO cortex exhibited reduced firing rates and lower functional connectivity, indicating altered network dynamics. Post-mortem analysis revealed higher neuron density in recorded cortical regions acutely and greater excitatory synapse density in CA1 ofFus^OLcKO mice without significant changes in myelin profiles.Significance. Fusdepletion in OLs enhances chronic hippocampal recordings but disrupts cortical network communication. These region-dependent effects highlight a differential role of OLs in supporting single-cell reliability versus population-level dynamics, offering novel insights into the interplay between oligodendrocytes, neural networks, and recording stability.