EXPERIMENTAL, CLINICAL AND MODELING STUDIES OF HUMAN OLFACTORY ADAPTATION

这个项目的总体目标是描述嗅觉适应和恢复的动态变化，并联系参与气味运输和清除的每个受体机制对这种变化的贡献。拟议的研究将通过实验和临床研究来追求这一目标，旨在阐明适应的范围和来源，并通过开发嗅觉适应的数学模型作为统一的框架。拟议研究的三个具体目标是：(1)评估参与气味传输和清除的周围感受器过程在多大程度上可以调节适应和恢复的时间进程；(2)表征作为一种功能和临床病因和年龄的挑战嗅觉系统的动态反应的变化，特别是在报告对环境和食物中介的气味快速和长期适应的临床患者中；(3)建立能够模拟气味在鼻/嗅区的传输、积累和清除的嗅觉适应的数学模型，如果合适的话，受体适应和恢复的时间进程(如项目1所示)。这个项目将增加我们对受体周围事件在短期和长期适应和恢复发展中的作用的理解。此外，通过与CCRC项目4的互动，我们将更好地了解适应中受体和受体周围事件之间的关系。该项目对在现实世界中补救动态嗅觉丧失的努力具有重要意义。虽然快速适应在临床评估中经常被报道，但目前对嗅觉功能障碍的临床评估不包括测量适应和恢复率的测试。然而，异常的适应或恢复速度可能会显著降低嗅觉敏感度，并使个人更容易受到气体泄漏、火灾和变质食物等危险的影响。异常的适应和/或恢复也可能会减少人们对食物的感知和享受，从而导致营养问题。对动态嗅觉丧失有显着影响的受体周围机制可能适用于治疗干预，以恢复嗅觉功能的某些方面。

The overall goal of this project is to describe the variation in the dynamics of olfactory adaptation and recovery, and to relate the contribution of per-receptor mechanisms involved in odorant transport and clearance to this variation. The proposed research will pursue this goal through experimental and clinical studies aimed at elucidating the range and sources of variation in adaptation, and by developing a mathematical model of olfactory adaptation to serve as a unifying framework. The three specific aims of the proposed research are: (1) to evaluate the extent to which peri-receptor processes involved in odorant transport and clearance can modulate the time-course of adaptation and recovery, (2) to characterize the variation in the dynamic response of a challenged olfactory system as a function and clinical etiology and age, especially among clinic patients who report rapid and prolonged adaptation to ambient and food-mediated odors, and (3) to develop a mathematical transport model of olfactory adaptation capable of simulating the odorant transport, accumulation and clearance in the nasal/olfactory region, and if appropriate, the time-course of receptor adaptation and recovery (as measured in Project 1). This project will increase our understanding of the role of peri-receptor events in the development of both short- and long-term adaptation and recovery. Moreover, through interactions with Project 4 in this CCRC we will obtain a better understanding of the relationship between receptor and peri-receptor events in adaptation. The project has important implications for efforts to remediate dynamic olfactory loss in real world situations. Although rapid adaptation is frequently reported in clinical evaluations, current clinical assessments of olfactory dysfunction do not include tests that measure rates of adaptation and recovery. However, abnormal rates of adaptation or recovery could significantly diminish olfactory sensitivity, as well as render individuals more vulnerable to hazards such as gas leaks, fires and spoiled food. Aberrant adaptation and/or recovery could also contribute to nutritional problems by reducing the perception and enjoyment of food. Peri-receptor mechanisms that contribute significantly to dynamic olfactory loss may be amenable to therapeutic interventions for restoring certain aspects of olfactory function.