The perception of odor blends and mixtures: Modulation, Inhibition and Enhancement of Olfactory Receptors alters perception of complex blends

对气味混合物和混合物的感知：嗅觉受体的调节、抑制和增强改变了对复杂混合物的感知

• 批准号: 10527337
• 负责人: Stuart J Firestein
• 金额: $ 33.91万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527337
• 关键词: Acetates; Acetophenones; Adopted; Afferent Neurons; Agonist; Allosteric Site; Area; Behavioral; Binding; Biological; Brain; Calcium; Cells; Characteristics; Chemical Structure; Chemicals; Chemistry; Classification; Code; Collection; Complex; Data; Development; Discrimination; Dissociation; Drug Industry; Epithelium; Event; Family; Funding; G-Protein-Coupled Receptors; Grant; Human; Image; In Situ; Individual; Investigation; Lead; Light; Medical; Microscopic; Microscopy; Molecular; Monitor; Nature; Neurons; Odors; Olfactory Pathways; Optics; Organic Chemistry; Pattern; Perception; Peripheral; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Psychophysics; Receptor Inhibition; Resolution; Sensory; Sensory Receptors; Signal Transduction; Smell Perception; Sorting; Stimulus; Structure; Techniques; Testing; Tissues; Visualization; Work; antagonist; body system; citral; drug development; experimental study; grasp; high throughput screening; hormone regulation; insight; neurotransmission; novel; olfactory receptor; olfactory stimulus; patch clamp; programs; receptor; receptor function; response; sensory system; side effect; signal processing; virtual

Project Summary/Abstract This is a continuation of an existing program funded by an RO1 that seeks to understand fundamental questions about the nature of the olfactory stimulus and its discrimination by primary sensory receptors, in order to better grasp the nature of the signal being forwarded to the brain. We supplement the standard organic chemistry approach to odor classification with one that includes a biological perspective based in principles of medicinal chemistry pioneered in the pharmaceutical industry and drug development. This allows us to not only consider physical chemical characteristics of molecules but also how they interact with the many olfactory receptors. This work, like much of olfactory cellular studies, utilized monomolecular stimuli to probe receptor function. However the olfactory system is usually confronted with complex stimulus blends of between tens and hundreds of components. To better understand the complexity of mixture discrimination we have begun utilizing a novel microscopic technique, SCAPE – that allows us to visualize large numbers of individual neurons in an intact tissue with single cell temporal and spatial resolution. Preliminary data from that work showed a remarkable and unexpected degree of inhibition and enhancement of responses by one component of the mixture on other components of the mixture. This raises a fundamental issue in olfactory discrimination as there appears to be considerable interaction between stimuli at the primary receptor, raising crucial questions about how the brain perceives and manages signals that differ depending on the presence of particular odors in a blend. It appears that many, if not all, odors can act as either an agonist or antagonist at different receptors. Thus depending on whether or not an antagonist to odor X, for example, exists in the blend, the signal from odor X will appear different to the brain. This level of complexity is unusual in sensory systems where signal processing of this sort occurs in the brain not the primary receptors. Understanding higher brain processing olfactory signals will require a greater understanding of the initial events at primary receptors. The olfactory code is more than the additive contributions of the olfactory receptors.

项目摘要/摘要 这是由RO1资助的现有计划的延续，该计划试图了解基本 有关嗅觉刺激的性质及其对原发感觉受体的歧视的问题， 为了更好地掌握被转发到大脑的信号的性质。我们补充标准 有机化学方法的气味分类方法，其中包括基于生物学的观点 医学化学原理在制药行业和药物开发中率先进行。这允许 我们不仅要考虑分子的物理化学特征，还考虑它们如何与许多分子相互作用 嗅觉受体。这项工作像大多数嗅觉细胞研究一样，利用单分子刺激来证明 受体功能。但是，嗅觉系统通常面临着复杂的刺激混合物 在数十至数百个组件之间。为了更好地了解混合歧视的复杂性，我们 已经开始使用一种新型的微观技术，Scape - 使我们能够可视化大量 具有单细胞临时和空间分辨率的完整组织中的单个神经元。初步数据 工作显示出一个显着且出乎意料的抑制程度和对反应增强的程度 混合物在混合物的其他组件上的组成部分。这引发了嗅觉的基本问题 歧视，因为在初级接收器处刺激之间似乎存在很大的相互作用， 关于大脑的百分比和管理信号的关键问题，这些信号取决于存在 混合中的特殊气味。看来许多（如果不是全部）气味可以充当激动剂或对手 不同的接收器。例如，取决于对异味X的拮抗剂是否存在 混合，来自气味X的信号将与大脑不同。这种复杂性水平在感觉上是不寻常的 这种信号处理的系统发生在大脑中，而不是主要受体。理解 较高的大脑处理嗅觉信号将需要更深入地了解初始事件 受体。嗅觉代码不仅仅是嗅觉受体的附加贡献。