INDIVIDUAL VARIATION IN OLFACTION

大约45-50%的成年人嗅觉正常， 能力不能闻到高浓度的雄烯酮， 天然存在的化合物，而其他人可以检测到气味， 低于200万亿分之一。 我们已经确定 这种敏感性的极端变化具有显著的遗传性， 成分 然而，对雄烯酮的敏感性不是 不可改变 随着年龄的增长，有一些变化，更引人注目的是， 广泛暴露于气味剂似乎诱导了一种能力， 检测它。在这个建议中，我们描述了一系列的人类和 动物模型研究旨在探索 基因对嗅觉的影响 对这种气味的体验。 使用标准的心理物理学 方法，我们建议探讨的性质的变化， 人类对雄甾烯酮的敏感性是由暴露于 气味剂也继续我们对发育因素研究 影响灵敏度。 我们还建议继续与 基因近交系小鼠来验证我们已经分离出 对雄烯酮不敏感的模型，并使用 标准的遗传学方法，估计遗传位点的数量， 参与调节对选定气味的敏感性， 确定我们是否可以增加老鼠对气味的敏感性 对他们不敏感。 这些研究将提供以下方面的基本信息： 哺乳动物嗅觉通过提供一个综合的研究因素 （遗传、发育和实验）可能影响 对气味敏感。 虽然在这方面取得了很大进展， 通过使用基因来理解感觉系统 方法，这些方法还没有得到充分利用， 鼻腔化学感受研究 事实上，嗅觉是一种 对经典感觉系统了解最少; 接收、转导和编码还有待于明确。 阐明。 研究人类和其他动物有选择性 这些缺陷可能有助于我们理解嗅觉 比如对色盲个体的研究 对色视觉的理解。

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.