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

Axons in the mammalian CNS fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) 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 long distances and re-innervate the brain. Analysis of genetically labeled RGCs revealed that 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 adulthood.

Contributions of Retinal Ganglion Cells to Subcortical Visual Processing and Behaviors.

Every aspect of visual perception and behavior is built from the neural activity of retinal ganglion cells (RGCs), the output neurons of the eye. Here, we review progress toward understanding the many types of RGCs that communicate visual signals to the brain, along with the subcortical brain regions that use those signals to build and respond to representations of the outside world. We emphasize recent progress in the use of mouse genetics, viral circuit tracing, and behavioral psychophysics to define and map the various RGCs and their associated networks. We also address questions about the homology of RGC types in mice and other species including nonhuman primates and humans. Finally, we propose a framework for understanding RGC typology and for highlighting the relationship between RGC type-specific circuitry and the processing stations in the brain that support and give rise to the perception of sight.