Cellular and Systems Neuroscience in the Treatment of Olfactory Dysfunction

嗅觉功能障碍往往被低估、未得到诊断和治疗，是影响五分之一个体生活质量下降的主要原因。有趣的是，反复短期接触气味剂可以恢复大约50%的患者的嗅觉功能，这在很大程度上独立于引发嗅觉功能丧失的原因。然而，这些收益背后的机制是完全未知的。本项目将探讨嗅觉训练的机制，并考虑其从周围的气味检测到大脑的气味编码的许多方面。我们的目标将通过结合动物模型的使用和对接受嗅觉训练的患者的人类样本的分析来实现，作为在临床相关背景下了解嗅觉基础生物学的一种手段。具体来说，本项目将研究嗅觉训练对以下方面的影响：1)啮齿动物和人类嗅觉上皮的细胞组成和分子特征；2)PNS神经干细胞活性和神经发生；3)大脑对气味编码的计算。每个方面都将通过汇集NSC和成人神经发生（Calegari），大脑嗅觉中心（Mizrahi）的神经生理学和嗅觉丧失（Hummel）的临床治疗方面的独特专业知识来解决。同时，嗅觉生物学将在分子、细胞和系统水平上进行研究，旨在确定这种基本感觉功能的基本机制，并设计更好的临床治疗方法。只有通过三个小组的多学科合作，才能实现这一雄心勃勃的项目。

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.