UC San Diego

Axons in the mammalian central nervous system (CNS) fail to regenerate after injury. A major goal of neuroscience is to develop strategies to promote axon regeneration and to re-establish accurate circuit connections. Using the mouse visual system as a model I show that neural activity of adult retinal ganglion cells (RGCs) induced by either visual experience or by chemogenetic activation, promotes axon regeneration after optic nerve crush. When combined with activation of the cell growth- promoting protein, mammalian target of rapamycin (mTOR), visual stimulation-driven RGC activity triggers axons to regenerate all the way back into the brain. Analysis of genetically-labeled RGC types revealed that remarkably, regrowth is target specific: RGC axons navigated back to their correct visual targets and avoided incorrect visual targets suggesting the guidance cues that direct RGC axons are either still present or are re- expressed in response to regeneration. Moreover, the target-specific regrowth of adult RGC axons resulted in partial recovery of several different visual functions. These findings indicate that visually-evoked and artificially-induced sensory activity can be powerful tools for enhancing axon regeneration and they highlight the remarkable capacity of mammalian CNS neurons to re-establish accurate circuit connections in the adult brain.