Forelimb Motor Learning and Memory Consolidation Drives Distinct Oligodendrocyte Plasticity to Regulate Task‐related Neuronal Activity

Genetic and chemical tracking of oligodendrogenesis, combining fiber photometric neuronal activity recording, reveals that distinct oligodendrocyte plasticities are adopted during different phases of motor learning to fine‐tune task‐related neuronal activity, with a preferential involvement of oligodendrogenesis suppression and node lengthening (type 2 oligodendrocyte plasticity) during learning and oligodendrogenesis enhancement (type 1 oligodendrocyte plasticity) during consolidation in a single pellet reaching task. Abstract Motor learning induces oligodendrocyte (OL) dynamics/plasticity during learning. However, it remains unclear whether different adaptive OL dynamics are required for different phases of motor learning and how they regulate neuronal activity. Here, we showed reduced oligodendrogenesis accompanied by elongated node length in the contra‐rostral forelimb area (cRFA) motor cortex during learning of the forelimb reaching task, both of which correlate with the learning performance. However, we observed increased oligodendrogenesis during the motor memory consolidation phase, which also correlates with the motor skill maintenance. Strikingly, Myrf conditional knockout (OPC‐Myrf‐cKO) mice, in which oligodendrogenesis can be artificially blocked, showed improved learning performance along with increased node length and increased task‐related neuronal activity in the cRFA when Myrf deletion (i.e., oligodendrogenesis blockade) is introduced prior to learning. However, they showed impaired rehearsal performance accompanied by decreased task‐related neuronal activity when gene deletion is induced after learning. These findings suggest that motor learning and consolidation may drive distinct OL plasticity to fine‐tune task‐related neuronal activity required at different phases. Genetic and chemical tracking of oligodendrogenesis, combining fiber photometric neuronal activity recording, reveals that distinct oligodendrocyte plasticities are adopted during different phases of motor learning to fine-tune task-related neuronal activity, with a preferential involvement of oligodendrogenesis suppression and node lengthening (type 2 oligodendrocyte plasticity) during learning and oligodendrogenesis enhancement (type 1 oligodendrocyte plasticity) during consolidation in a single pellet reaching task. Abstract Motor learning induces oligodendrocyte (OL) dynamics/plasticity during learning. However, it remains unclear whether different adaptive OL dynamics are required for different phases of motor learning and how they regulate neuronal activity. Here, we showed reduced oligodendrogenesis accompanied by elongated node length in the contra-rostral forelimb area (cRFA) motor cortex during learning of the forelimb reaching task, both of which correlate with the learning performance. However, we observed increased oligodendrogenesis during the motor memory consolidation phase, which also correlates with the motor skill maintenance. Strikingly, Myrf conditional knockout (OPC- Myrf -cKO) mice, in which oligodendrogenesis can be artificially blocked, showed improved learning performance along with increased node length and increased task-related neuronal activity in the cRFA when Myrf deletion (i.e., oligodendrogenesis blockade) is introduced prior to learning. However, they showed impaired rehearsal performance accompanied by decreased task-related neuronal activity when gene deletion is induced after learning. These findings suggest that motor learning and consolidation may drive distinct OL plasticity to fine-tune task-related neuronal activity required at different phases. Advanced Science, Volume 12, Issue 48, December 29, 2025.