INDIVIDUAL VARIATION IN OLFACTION

嗅觉正常的成年人中，大约有45%-50% 能力不能闻到高浓度的雄烯酮，一种 自然产生的化合物，而其他人可以在 空气中的比例不到万亿分之200。我们已经确定 这种敏感度的极端变异具有显著的遗传 组件。然而，对雄烯酮的敏感性不是 一成不变。随着年龄的增长，情况也会发生变化，更引人注目的是， 大量接触这种气味似乎会诱导一种能力 发现它。在这份提案中，我们描述了一系列人类和 动物模型研究旨在探索两者之间的相互作用 基因对嗅觉能力的影响及其影响 对那股气味的体验。使用标准的心理物理学 方法，我们建议探索这些变化的性质 人体对雄性烯酮的敏感性 香料也在继续我们对发育因素的研究 影响敏感度。我们还建议继续与 基因近亲繁殖的小鼠品系，以验证我们已经分离出 雄激素不敏感模型的建立及其应用研究 标准遗传方法，用于估计遗传基因座的数量 参与调节对选定气味的敏感性，并 确定我们能否提高小鼠对气味的敏感度 被发现对他们不敏感。 这些研究将提供以下基本信息： 哺乳动物嗅觉对多种因素的综合研究 (遗传、发育和实验)可能会影响 对气味敏感。虽然在以下方面取得了很大进展 通过使用基因来理解感觉系统 方法，但这些方法在 鼻腔化学感受的研究。事实上，嗅觉是 对经典感官系统知之甚少； 信号的接收、转导和编码尚不清楚 已澄清。对人类和其他动物的研究具有选择性 缺陷可能对我们对嗅觉的理解有很大帮助 就像对色盲个体的研究一样，我们的 对色觉的理解。

Roughly 45-50% of human adults with otherwise normal olfactory abilities cannot smell high concentrations of androstenone, a naturally occurring compound, while others can detect an odor at less than 200 parts per trillion in air. We have determined that this extreme variation in sensitivity has a significant genetic component. However, sensitivity to androstenone is not immutable. There are changes with age, and more striking, extensive exposure to the odorant appears to induce an ability to detect it. In this proposal we describe a series of human and animal model studies designed to explore the interaction between the genetic influence on ability to detect an odor and the effects of experience with that odor. Using standard psychophysical methods, we propose to explore the nature of the changes in human sensitivity to androstenone which is induced by exposure to the odorant as well continue our studies on developmental factors affecting sensitivity. We also propose to continue to work with genetically inbred strains of mice to verify that we have isolated a model for insensitivity to androstenone and study it using standard genetic methods, to estimate the number of genetic loci involved in regulating sensitivity to selected odorants, and to determine whether we can increase sensitivity to odorants in mice found to be insensitive to them. These studies will produce fundamental information on mammalian olfaction by providing an integrated study of factors (genetic, developmental and experimental) that may influence sensitivity to odorants. While much progress has been made in understanding sensory systems through the use of genetic methods, these approaches have not been fully exploited in the study of nasal chemoreception. Indeed, olfaction is one of the least understood of the classical sensory systems; mechanisms of reception, transduction, and coding have yet to be clearly elucidated. Studies of people and other animals having selective deficits may contribute to our understanding of olfaction much like studies of color-blind individuals have contributed to our understanding of chromatic vision.