Perceptual Effects of Odorant Antagonists

气味拮抗剂的感知效果

基本信息

批准号：
10638507
负责人：
Timothy S McClintock
金额：
$ 18.81万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10638507
关键词：
Affect Amines Anterior nares Binding Brain CNS processing Cigarette Code Collaborations Complex Data Detection Development Discrimination Elements Experimental Designs Family Future Health Home Human Human Biology Institution Knowledge Latrine Learning Mammals Measures Mentors Molecular Mus Odorant Receptors Odors Outcome Pattern Perception Performance Peripheral Pharmacology Physiology Positioning Attribute Procedures Psychophysics Quality of life Research Research Personnel Research Project Grants Rodent Role Shapes Signal Transduction Smell Perception Smoke Social Interaction Technology Testing Training Translational Research Translations Visualization Volatilization Work antagonist behavior test combinatorial craving efficacy testing experimental study human subject improved in vivo learning strategy neural pharmacologic pre-clinical preclinical study programs receptor receptor function recruit response signal processing stem tool translational potential

项目摘要

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.

摘要/摘要麦克林托克博士对气味反应受体功能的研究使用了一种技术同时测量所有 1,100 个气味受体 (OR) 和所有 14 种痕量胺的反应相关受体（TAAR）与自由行为小鼠的气味相关，捕获受体反应模式这些模式通常称为组合代码，负责气味识别和气味识别。该技术量化了 OR 和 TAAR 的响应和响应损失，因此这些研究的一个主要主题是调查气味相互作用在塑造反应模式中的作用。这些相互作用很常见，而且由于气味总是几乎是许多不同气味剂的混合物，这些发现预测气味相互作用对于气味的编码和感知至关重要哺乳动物的这些受体相互作用是否能正确预测感知效应，尤其是在人类中。目前尚不清楚，因此感知效应的研究代表了一种评估机械共性的方法研究这些相互作用如何影响人类的气味感知通常对于理解很重要。神经编码和拮抗剂相互作用是未来研究气味信号处理的宝贵工具此外，气味相互作用也具有转化潜力。对对人类健康和生活质量产生负面影响的恶臭的看法。机遇激发了药理学工具的开发工作，以改变特定的反应 OR 和 TAAR 并操纵对某些气味的感知，从而训练人类嗅觉。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气味相互作用，以测试这些相互作用是否是与人类共有的机制以及是否某些气味相互作用对人类具有转化效用。