Perceptual Effects of Odorant Antagonists

摘要/摘要 麦克林托克博士对感受器对气味的反应功能的研究使用了一种技术， 同时测量所有1100种气味感受器(OR)和所有14种痕量胺的反应 与气味相关的受体(TAAR)在行为自由的小鼠中，捕捉到 将气味编码。这些模式，通常被称为组合码，负责气味识别和 歧视。这项技术量化了来自ORS和TAAR的响应和响应损失，因此 这些研究的主要主题是调查气味相互作用在塑造反应模式中的作用。 这些相互作用是很常见的，因为气味几乎总是许多不同气味的混合物， 这些发现预测，气味的相互作用是编码和感知气味的基础 哺乳动物。受体上的这些相互作用是否正确地预测了感知效果，特别是在人类身上，是 由于尚不清楚，因此对知觉效果的研究代表了一种评估机械共性的方法 人类。研究这些相互作用如何影响气味感知通常对理解 神经编码和拮抗剂相互作用是未来气味信号处理研究的有价值的工具。 大脑。此外，气味相互作用也具有翻译潜力。最好的例子就是阻止 对对人类健康和生活质量有负面影响的恶臭的感知。这些可翻译的 机遇推动了开发药理工具以修改特定反应的工作 ORS和TAAR，从而操纵对某些气味的感知。人类嗅觉训练 本申请中提出的心理物理学将使麦克林托克博士能够利用他的临床前数据 将气味相互作用转化为测试这些相互作用是否是与人类共享的机制，以及 某些气味相互作用对人类有翻译作用。

Summary/Abstract Dr. McClintock’s research on the function of receptors responsive to odors uses a technology that simultaneously measures the responses of all 1,100 odorant receptors (ORs) and all 14 trace-amine associated receptors (TAARs) to odors in freely behaving mice, capturing the receptor response patterns that encode odors. These patterns, often called combinatorial codes, are responsible for odor identification and discrimination. This technology quantifies both response and loss of response from ORs and TAARs so a major theme of these studies is investigating the role of odorant interactions in shaping response patterns. These interactions are common, and because odors are nearly always mixtures of many different odorants, these findings predict that odorant interactions are fundamental to the encoding and perception of odors in mammals. Whether these interactions at receptors correctly predict perceptual effects, especially in humans, is as yet unknown so studies of perceptual effects represent a way to assess mechanistic commonality with humans. Investigating how these interactions affect odor perception is generally important for understanding neural coding and antagonist interactions are valuable tools for future studies of odor signal processing in the brain. In addition, odorant interactions also have translational potential. Prime examples are blocking perception of malodors that have negative impacts on human health and quality of life. These translational opportunities motivate work on the development of pharmacological tools to modify responses from specific ORs and TAARs and thereby manipulate the perception of certain odors. Training in human olfactory psychophysics proposed in this application will put Dr. McClintock in position to leverage his preclinical data on odorant interactions into tests of whether these interactions are mechanisms shared with humans and whether certain odorant interactions have translational utility in humans.