Neurogenesis is required for behavioral recovery after injury in the visual system ofXenopus laevis

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Nonmammalian vertebrates have a remarkable capacity to regenerate brain tissue in response to central nervous system (CNS) injury. Nevertheless, it is not clear whether animals recover lost function after injury or whether injury- induced cell proliferation mediates recovery. We address these questions using the visual system and visually- guided behavior in Xenopus laevis tadpoles. We established a reproducible means to produce a unilateral focal injury to optic tectal neurons without damaging retinotectal axons. We then assayed a tectally- mediated visual avoidance behavior to evaluate behavioral impairment and recovery. Focal ablation of part of the optic tectum prevents the visual avoidance response to moving stimuli. Animals recover the behavior over the week following injury. Injury induces a burst of proliferation of tectal progenitor cells based on phospho- histone H3 immunolabeling and experiments showing that Musashi- immunoreactive tectal progenitors incorporate the thymidine analog chlorodeoxyuridine after injury. Pulse chase experiments indicate that the newly- generated cells differentiate into N- β - tubulin- immunoreactive neurons. Furthermore, in vivo time- lapse imaging shows that Sox2- expressing neural progenitors divide in response to injury and generate neurons with elaborate dendritic arbors. These experiments indicate that new neurons are generated in response to injury. To test if neurogenesis is necessary for recovery from injury, we blocked cell proliferation in vivo and found that recovery of the visual avoidance behavior is inhibited by drugs that block cell proliferation. Moreover, behavioral recovery is facilitated by changes in visual experience that increase tectal progenitor cell proliferation. Our data indicate that neurogenesis in the optic tectum is critical for recovery of visually- guided behavior after injury. J. Comp. Neurol. 521:2262– 2278, 2013. © 2012 Wiley Periodicals, Inc.Although amphibians are known for their regenerative response to brain injury, it is unclear whether recovery of behavioral deficits requires neurogenesis. We report that focal injury of the optic tectum Xenopus tadpoles prevents behavioral avoidance to moving stimuli, yet animals recover after one week. Injury induces proliferation of tectal progenitors that generate neurons. Blocking cell proliferation inhibits recovery, and changes in visual experience that increase neurogenesis facilitate recovery, indicating that neurogenesis is critical for recovery of visually- guided behavior after injury.

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