The Peripheral Representation of Odor Space

气味空间的外围表征

• 批准号: 10670076
• 负责人: Thomas Bozza
• 金额: $ 72.16万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670076
• 关键词: Affinity; Animals; Bar Codes; Biological Assay; Biology; Brain; Calcium; Chemicals; Code; Color; Color Perception; Color Visions; Data; Data Set; Dimensions; Exposure to; Family; Foundations; Functional Imaging; Genetic; Genomics; Goals; Human; Image; Individual; Knowledge; Ligands; Link; Logic; Mammals; Maps; Measures; Methods; Modeling; Modernization; Molecular; Mus; Nature; Odorant Receptors; Odors; Olfactory Pathways; Pattern; Perception; Peripheral; Property; Receptor Down-Regulation; Receptor Gene; Sampling; Sensory; Smell Perception; Specificity; Statistical Methods; Stimulus; Structure; System; Techniques; Technology; Testing; Time; analytical tool; awake; combinatorial; data tools; experimental study; genome sequencing; in vivo; interdisciplinary approach; neural; novel; novel strategies; olfactory bulb; olfactory receptor; olfactory stimulus; physical property; predicting response; predictive modeling; rational number; receptor; receptor downregulation; recruit; response; sensory system; spatiotemporal; theories; transcriptome sequencing; transcriptomics; transmission process

Summary (Project 1: The peripheral representation of odor space) Progress towards an understanding of olfactory coding has been hampered by long-standing hurdles created by the nature of the stimulus and the complexity of the underlying sensory biology. At the same time, a description of olfactory coding in mammals would provide a unique window into how multidimensional stimuli are represented by the mammalian brain. Olfactory systems use large families of odorant receptors to detect a vast number of chemical stimuli. An important challenge that must be overcome to better understand olfaction is to establish a comprehensive description of what features of olfactory stimuli are represented by the system. Doing so requires that we overcome previously insurmountable technical challenges in identifying the stimulus specificity of a large number of receptors to a large number of odorants, and that we generate a theoretical framework for quantifying and exploring the multidimensional “space” of odors and receptors. Here, we propose an interdisciplinary effort to comprehensively characterize the odorant response properties of a large number of odorant receptors in vivo, and to use this information to explicitly and rigorously test novel models of odor coding. This project exploits the one-to-one correspondence between odorant receptors and glomeruli in the olfactory bulb of mice. Aim 1 will characterize the sensitivities of a large number of receptors (glomeruli) in awake, intact animals using functional imaging. Aim 2 will map these glomerular responses to specific receptors using emerging spatial transcriptomics methods. Aim 3 will use a powerful genomics-based assay to identify the highest affinity receptors for a large set of individual odors. Aim 4 will test a novel theoretical framework for understanding how odor features are represented. This large-scale in vivo multidisciplinary approach will provide long-sought data and analytical tools to rigorously explore potential models of odor coding.

总结（项目1：气味空间的外围表征） 对嗅觉编码理解的进展一直受到长期存在的障碍的阻碍， 刺激的性质和潜在的感觉生物学的复杂性。与此同时， 哺乳动物嗅觉编码的研究将提供一个独特的窗口，了解多维刺激是如何 以哺乳动物的大脑为代表。嗅觉系统使用大家族的气味受体来检测大量的 化学刺激的数量。为了更好地理解嗅觉，必须克服的一个重要挑战是 建立一个系统所代表的嗅觉刺激特征的综合描述。做 因此，我们需要克服以前在确定刺激措施方面无法克服的技术挑战 大量受体对大量气味的特异性，我们产生了一个理论上的 量化和探索气味和受体的多维“空间”的框架。在这里，我们建议 一个跨学科的努力，以全面表征气味的反应特性，大量的 气味受体在体内，并使用这些信息明确和严格的测试气味编码的新模型。 这个项目利用嗅觉中气味受体和肾小球之间的一一对应关系 小鼠的鳞茎。目的1将描述大量受体（肾小球）在清醒、完整的 使用功能成像的动物。目的2将绘制这些肾小球反应的具体受体， 新兴的空间转录组学方法。Aim 3将使用一种强大的基于基因组学的检测方法来识别 最高亲和力的受体为一大套个人的气味。Aim 4将测试一个新的理论框架， 了解气味特征是如何表现的。这种大规模的体内多学科方法将提供 长期寻求的数据和分析工具，以严格探索气味编码的潜在模型。