Cellular and Systems Neuroscience in the Treatment of Olfactory Dysfunction

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While often underestimated, undiagnosed and untreated, olfactory dysfunctions are a main cause of a reduced quality of life affecting one in five individuals. Interestingly, repeated short-term exposures to odorants can rescue olfactory function in about 50% of patients largely independently from the causes that triggered its loss. Yet, the mechanisms behind these gains are completely unknown. This project will address the mechanisms underlying olfactory training and considering its many aspects from odor detection by the perifery to odor encoding by the brain. Our goal will be pursued by combining the use of animal models and analysis of human samples from patients undergoing olfactory training as a means to understand the basic biology underlying olfaction in a clinically relevant context.Specifically, this project will investigate the effects of olfactory training on the i) cellular composition and molecular signature of the rodents and human olfactory epithelium, ii) neural stem cell activity and neurogenesis in the PNS and iii) computation of odor encoding by the brain. Each aspect will be addressed by bringing together unique expertise in the molecular characterization and manipulation of NSC and adult neurogenesis (Calegari), neurophysiology of the brain’s olfactory centers (Mizrahi) and clinical treatment of olfactroy loss (Hummel). Together, the biology of olfaction will be investigated at the molecular, cellular and systemic level aiming to identify the basic mechanisms underlying this fundamental sensory function and design of better clinical treatments. Only by the multidisciplinary collaboration of the three groups can this ambitious project be pursued.