Structural regeneration and functional recovery of the olfactory system of adult zebrafish following brain injury

Olfactory dysfunction is a common outcome of brain injuries, negatively affecting quality of life. The adult mammalian nervous system has limited capacity for olfactory recovery, making it challenging to study olfactory regeneration and recovery. In contrast, zebrafish are ideal for such studies due to its extensive and lifelong regenerative abilities. In this work, we describe a model of excitotoxic injury in the olfactory bulb using quinolinic acid lesions in adult zebrafish of both sexes. We observed extensive neurodegeneration in both the olfactory bulb and olfactory epithelium, including a reduction of bulbar volume, neuronal death, and impaired olfactory function. Recovery mechanisms involved tissue remodeling, cell proliferation, neurogenesis, leading to full restoration of olfactory function by 21 days. This study provides a model to further investigate the effects of excitotoxicity on olfactory dysfunction, and highlights zebrafish’s remarkable regenerative abilities, providing insights into potential therapeutic strategies for restoring olfactory function following brain injuries. Significance Statement This study addresses the critical issue of olfactory dysfunction following brain injury, and provides insight into regenerative mechanisms by leveraging the unique regenerative abilities of adult zebrafish. The novelty of our study lies in its comprehensive and integrated characterization of structural and functional recovery across the olfactory system and the contribution of telencephalic inflammation and neurogenesis in recovery. Furthermore, our results offer compelling evidence for a mechanistic link between excitotoxic brain damage and olfactory dysfunction, a poorly understood relationship. This work describes a novel model to further our understanding of fundamental principles of central and peripheral neural regeneration and plasticity in vertebrates, an emerging and exciting topic in neuroscience.