Forelimb motor learning and memory consolidation drives distinct oligodendrocyte plasticity to fine-tune task-related neural activity

Previous work has shown that “complex wheel” running requires new oligodendrocyte (OL) generation. Here, we ask whether adaptive OL plasticity occurs during a dexterous forelimb reaching task. Surprisingly, a decrease in oligodendrogenesis is observed after motor learning, accompanied by an increase in the length of Ranvier node in the contra-rostral forelimb area (cRFA) motor cortex. We then observe an increase in subsequent OPC proliferation and maturation during skill memory consolidation. Genetic blockade of oligodendrogenesis in Myrf conditional-knockout (Myrf-cKO) mice prior to reaching task results in enhanced rather than impaired learning, whereas blockade during the memory phase impairs motor skill retention. In vivo recordings of task-related calcium dynamics show that Myrf-cKO mice exhibit increased movement-related calcium activity and an increased number of cFos-expressing neurons in the cRFA during learning, but reduced neuronal reactivation during skill recall. These findings suggest forelimb motor learning and consolidation may drive distinct OL dynamics/plasticity to fine-tune task-related neural activity.