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


ABSTRACT: 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.

SUBMITTER: Lim JH 

PROVIDER: S-EPMC5708130 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Lim Jung-Hwan A JH   Stafford Benjamin K BK   Nguyen Phong L PL   Lien Brian V BV   Wang Chen C   Zukor Katherine K   He Zhigang Z   Huberman Andrew D AD  

Nature neuroscience 20160711 8


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  ...[more]

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