Abstract
Approximately
half of the human brain consists of myelinated axons. Central nervous
system (CNS) myelin is made by oligodendrocytes and is essential for
nervous system formation, health, and function. Once thought simply as a
static insulator that facilitated rapid impulse conduction, myelin is
now known to be made and remodeled in to adult life. Oligodendrocytes
have a remarkable capacity to differentiate by default, but many aspects
of their development can be influenced by axons. However, how axons and
oligodendrocytes interact and cooperate to regulate myelination in the
CNS remains unclear. Here, we review recent advances in our
understanding of how such interactions generate the complexity of
myelination known to exist in vivo. We highlight intriguing results that
indicate that the cross-sectional size of an axon alone may regulate
myelination to a surprising degree. We also review new studies, which
have highlighted diversity in the myelination of axons of different
neuronal subtypes and circuits, and structure-function relationships,
which suggest that myelinated axons can be exquisitely fine-tuned to
mediate precise conduction needs. We also discuss recent advances in our
understanding of how neuronal activity regulates CNS myelination, and
aim to provide an integrated overview of how axon-oligodendrocyte
interactions sculpt neuronal circuit structure and function.
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