Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain

Axonal myelin increases neural processing speed and efficiency. In adulthood, it is not known if patterns of myelin distribution are fixed or if myelinating oligodendrocytes are continually generated and maintain the capacity for structural remodeling. Using high-resolution intravital label-free and fluorescence optical imaging in the mouse cortex, we demonstrate lifelong oligodendrocyte generation occurring in parallel with structural plasticity of individual myelin internodes. Continuous internode formation occurred on both partially myelinated and unmyelinated axons and the total myelin coverage along individual axons progressed up to two years of age. After peak myelination, gradual oligodendrocyte death and myelin degeneration in aging were associated with pronounced internode loss and myelin debris accumulation within microglia. Thus, cortical myelin remodeling is protracted throughout life, potentially playing critical roles in neuronal network homeostasis. The gradual loss of internodes and myelin degeneration in aging could contribute significantly to brain pathogenesis.