title: Adult axolotls can regenerate original neuronal diversity in response to brain injury.
abstract: The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Amamoto
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, United States.
authors.forename: Violeta Gisselle Lopez
authors.initials: VG
authors.lastname: Huerta
authors.affiliation: Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, United States.
authors.forename: Emi
authors.initials: E
authors.lastname: Takahashi
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, United States.
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.affiliation: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Grant
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, United States.
authors.forename: Zhanyan
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, United States.|Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, United States.
authors.forename: Paola
authors.identifier: 0000-0003-2184-2277
authors.initials: P
authors.lastname: Arlotta
mesh_terms: D000558:Ambystoma mexicanum; D000818:Animals; D001921:Brain / Q000502:physiology*; D001930:Brain Injuries; D012038:Regeneration
keywords: Axolotl; brain regeneration; developmental biology; neuronal diversity; neuroscience; stem cells