Olfactory Training Enhances Adult Neurogenesis of the Olfactory Epithelium Improving Odor Discriminability of the Olfactory Bulb

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SUMMARY Olfaction enables us to detect chemicals in the environment, and its impairment affects one in four people worldwide. As the most common therapy, olfactory training involves repeated exposure to odorants restoring function in 30-50% of patients. However, the mechanisms underlying this therapy, and its partial efficacy, are unknown. By modelling olfactory training in mice, we found that odor exposure triggers quiescent neural stem cells of the olfactory epithelium to re-enter the cell cycle, enhancing neurogenesis and survival of olfactory sensory neurons. Coupling neuronal activity with stem cells proliferation, these effects scaled with odor concentration and were replicated without odorants upon chemogenetic activation of olfactory sensory neurons. Imaging mitral cells in the olfactory bulb revealed that increased neurogenesis in the olfactory epithelium enhanced odor sensitivity and discriminability. Our findings uncover activity-dependent cellular mechanisms linking peripheral nervous system regeneration to central olfactory processing, offering new avenues for treating olfactory dysfunction. GRAPHICAL ABSTRACT HIGHLIGHTS - Olfactory training (OT) is a common clinical practice of unknown cellular mechanisms - OT in mice triggers stem cell activation and neurogenesis in the olfactory epithelium - Artificial stimulation of olfactory neurons is sufficient to trigger neural stem cell activity - Neurogenesis in the olfactory epithelium improves odor discrimination by mitral cells

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