Cortical white matter: no longer a silent partner.

This takes the position that the cell-sparse cortical white matter (WM) of gyrencephalic brains has too long held a secondary place in neuroanatomical investigations of cell-dense gray matter (GM) regions. This is unjustified and even problematic because WM, like GM, has its own subcellular, cellular, and supracellular multi-scale organization. Axons are not passive cables or wires, but engage in multiple processes, some in cooperation with neurons in the GM and, as increasingly recognized, also inter- and intra-axonal. In five sections of this review, we revisit traditional assumptions about WM organization and touch on recent results regarding: the axonal cytoskeleton and myelination, neuroanatomical approaches to global WM organization, open issues about "endpoints" (i.e., origin and termination of axon bundles), and orderly vs. "scrambled" topographies. There has been significant research progress at all spatial scales, and there is good reason to anticipate a more holistic approach in the next stages that will bring WM investigations more in line with the integrative approaches already customary in GM investigations.