The human brain with about 1011 neurons and about 1015 connections in addition to neuroglia which consists of even more numerous cells of various types is one of the most complex and fascinating systems in the universe. The connections between neurons are established through axons, which are long and often thin structures that carry electrical signals also called action potentials. Physiologic function relies on correct timing of the arrival of the electric signals and hence speed at which they travel along the axons, which, in turn, depends strongly on the diameter of the axon, which therefore must be precisely matched to its physiologic function.
The principal determinant of axon diameter in vertebrates are space-filling cytoskeletal polymers called neurofilaments (NFs). Morphometric studies have indeed established a direct correlation between NFs and axonal diameter. In addition to their space-filling role, NFs are also cargo of slow axonal transport and are in relentless but slow movement toward the nerve terminals. The focus of our collaborative research with the Brown-lab at Ohio State University is a new paradigm for the understanding of axon morphology that is rooted in the dual motile and architectural function of NFs as cargo of slow transport and space-filling structures. According to this view, axon caliber is emergent and dynamically determined by changes in the flow of NFs. We combine fluorescent life imaging methods to characterize the dynamics of the cytoskeleton of the axon, with mathematical and computational modeling to understand how axon caliber is regulated, how morphological structures, such as constrictions at nodes of Ranvier or neurodegenerative disease related swellings, are formed.
