Rebooting functional integration of neurons following injury in the aged African turquoise killifish

Age-related neurodegenerative diseases have become a frequent cause of death in modern society since there are still no effective treatments available. To recover from the associated neuron loss, a large induction of adult neurogenesis, or neuroregeneration, is needed. Although new neurons are born in the adult vertebrate CNS, they often fail to successfully integrate in the aged non-permissive circuit. The fundamental processes underlying this aging-induced failure is what I aim to study using a novel gerontology model; the African turquoise killifish. Via stab-injury in the Dm telencephalon, I will assess the impact of aging on newborn neuron, dendrite and synapse maturation as well as integration and activity. I will use differential transcriptomics to reveal novel pathways to modulate in order to rejuvenate dendrite dynamics in an aged environment and induce adequate circuit integration. Validation of these pathways will be judged on an in vitro compound testing platform, in vivo and via an operant learning and memory test. The outcome of this project will provide new potential strategies to boost successful integration and maturation of newborn neurons after neuron loss, paving the way towards full recovery of the aged diseased brain.