title: 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.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Jung-Hwan A
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Stafford
authors.affiliation: Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: Phong L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Lien
authors.affiliation: Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Animal, Dairy and Veterinary Sciences Department, Utah State University, Logan, Utah, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zukor
authors.affiliation: Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, California, USA.|Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Huberman
mesh_terms: D000375:Aging; D000818:Animals; D001369:Axons / Q000502:physiology*; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases