Mouse white matter matters: cortical origins and spatial organization of mouse white matter tracts.

White matter—the fundamental structure underlying network connectivity—lies at the heart of the brain’s computational power. White matter is organized into fiber tracts, or bundles, in both human and nonhuman primate brains. These bundles consist of long-range axonal projections with a set of shared origin and termination points and exhibit a predictable organization. However, the organization of white matter in the mouse brain remains relatively unknown. This knowledge gap is surprising given the central role of mice in neuroscience, with mouse brains serving as the dominant model for transgenics, in vivo calcium imaging, and circuit manipulation. To address this gap, we used the Allen Mouse Brain Connectivity Atlas of anterograde tract-tracing experiments to ask about the organization of mouse white matter. Specifically, we evaluated which cortical regions used which bundles and then examined the topographic organization of each bundle—i.e., whether projections from distinct cortical regions occupied distinct spatial areas within each tract according to cortical origin. We found that many mouse white matter tracts—including the corpus callosum, internal capsule, and cingulum bundle—were highly topographically organized. For both the internal capsule and cingulum bundle, this topographic organization means that specific mouse white matter bundles can be targeted to model treatment of brain disorders. Our findings help link mouse models of neurological disease and treatment with human brain disorders and interventions.