Long-range axon branching: contributions to brain network plasticity and repair

Brain function requires exquisitely adapted plasticity at multiple scales, from synapses to whole-brain networks. Evidence for large-scale plasticity in functional brain networks comes from neuroimaging data across a variety of species, particularly during development and following injury. However, how large-scale network remodelling is achieved at the microscopic level is unknown as the growth of entirely new long-distance axons is unlikely to occur. Recent insights from electron microscopic connectome studies and single-cell projectomes of neurons in the brains of multiple model organisms have provided new evidence for the incredible structural complexity of axons and their branches that traverse the brain. This evidence shows highly arborized axonal projections, differentially myelinated branches of the same axon, and axonal regions devoid of synaptic contacts but with the potential to form synaptic connections in new or additional areas. Recent electron microscopic data suggest that these axonal features may be evolutionarily conserved. Here we consider whether these features could enable long-range and large-scale neuroplastic changes at a functional level, particularly following focal brain injury. These insights contribute to our emerging understanding of how the brain undergoes large-scale reorganization to adapt to changing circumstances.