Neural activity promotes long distance, target-specific regeneration of adult retinal axons

Abstract

Axons in the mammalian central nervous system (CNS) fail to regenerate after injury. Here we show that if retinal ganglion cell (RGC) activity is increased by visual stimulation or using chemogenetics, their axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate the long distances necessary to re-innervate the brain. Analysis of genetically-labeled RGCs revealed this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in the adult brain.