Axon plasticity in the mammalian central nervous system after injury

•Neuron-extrinsic and -intrinsic factors regulate axon plasticity.•Circuit rewiring involves formation of detour circuits or activation of latent tracts.•Rehabilitation may strengthen adaptive connections after injury.•Transneuronal tracing and 3D imaging may reveal post-injury network alterations.

It is widely recognized that severed axons in the adult central nervous system (CNS) have limited capacity to regenerate. However, mounting evidence from studies of CNS injury response and repair is challenging the prevalent view that the adult mammalian CNS is incapable of structural reorganization to adapt to an altered environment. Animal studies demonstrate the potential to achieve significant anatomical repair and functional recovery following CNS injury by manipulating axon growth regulators alone or in combination with activity-dependent strategies. With a growing understanding of the cellular and molecular mechanisms regulating axon plasticity, and the availability of new experimental tools to map detour circuits of functional importance, directing circuit rewiring to promote functional recovery may be achieved.