Developmental Profiling of Structural and Functional Maturation in Mouse Corpus Callosum

ABSTRACT As the largest white matter tract within the central nervous system (CNS) to connect two cerebral hemispheres, the corpus callosum axon bundle consists of a mixture of myelinated and unmyelinated axons and plays a crucial role in executing sensory, motor and cognitive functions within the CNS. In this study, we comprehensively characterized progressive alterations in myelination and oligodendrocyte lineage cell densities during the postnatal myelin development and then correlated these structural dynamics to the maturation of axonal impulse conduction within the mouse corpus callosum. In addition, we found that the extracellular spaces between callosal axons were significantly reduced during the first three postnatal weeks in mice, while micron‐scale diffusion of small molecule within this region remained largely unaffected and displayed isotropy. However, the glutamate transporter GLT‐1 was markedly upregulated within the first 3 postnatal weeks, and its expression was found not only in astrocytes but also in oligodendrocyte lineage cells. Finally, we showed that the ectopic callosal axonal vesicle machinery were not fully matured until the later state of myelin development. In summary, our study provided a dynamic profile of the structural and functional maturation of mouse corpus callosum during postnatal myelin development.