Longitudinal tractography of the mouse corpus callosum reveals topographical order and differences due to sex and aging

The corpus callosum (CC) is the major tract connecting the two hemispheres in placental mammals and diffusion-weighted (DWI) MRI has revealed the meso/macroscopic organization of human CC and its organization of connectivity with the cortex. Here, we applied longitudinal DWI probabilistic tractography to study the CC fibers of mice across the adult lifespan. Our results reveal that connections of eight cortical areas can be delineated within the CC. The mouse CC organization aligns with the human topographical organization with frontal areas occupying the genus and parieto-occipital the posterior splenium region. A further regional analysis of passage fields showed stable field sizes in many of the studied areas over time. In contrast, several areas of the mouse default mode network and motor cortical regions show a decline in size with advancing age. Our analysis also identifies sex differences in the CC with female mice showing a larger orbitofrontal commissural connection. In summary, we confirm a mammalian-like organization of the CC in mice. Furthermore, we confirm an aging-related decline in the integrity of mouse white matter that aligns with previous findings in humans, thus opening up the possibility for future developmental in vivo studies across the entire lifespan using a mouse model.