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

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

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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 McClintock博士对反应气味的接收功能的研究使用了一种技术类似地测量所有1,100个气形受体（OR）和所有14个痕量胺的响应相关的接收器（TAARS）与自由行为的小鼠的气味，捕获受体反应模式编码气味。这些模式，通常称为组合代码，负责气味识别和歧视。该技术量化了ORS和TAARS的响应和反应丧失，因此这些研究的主要主题正在研究Odorint相互作用在塑造响应模式中的作用。这些相互作用很常见，并且由于气味几乎总是许多不同气味的混合物，所以这些发现预测，气形相互作用是对气味的编码和感知的基础哺乳动物。这些受体上的这些相互作用是否正确预测感知效应，尤其是在人类中，是尚未知道人类。研究这些相互作用如何影响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对未来对气味信号处理的研究的宝贵工具脑。此外，Odorint相互作用也具有翻译潜力。主要的例子正在阻止对对人类健康和生活质量产生负面影响的疾病的感知。这些翻译机会动机工作开发了制药工具，以修改特定的反应 ORS和TAARS，从而操纵某些气味的感知。人类嗅觉培训在本申请中提出的心理物理学将使麦克林托克博士处于适当的位置，以利用他的临床前数据对于这些相互作用是否是与人共享的机制以及是否是否某些异常相互作用在人类中具有转化效用。