The Peripheral Representation of Odor Space

气味空间的外围表征

• 批准号: 10200165
• 负责人: Thomas Bozza
• 金额: $ 73.97万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200165
• 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 Gene; Sampling; Sensory; Smell Perception; Specificity; Statistical Methods; Stimulus; Structure; System; Techniques; Testing; Time; analytical tool; awake; base; combinatorial; data tools; experimental study; genome sequencing; in vivo; interdisciplinary approach; novel; novel strategies; olfactory bulb; olfactory receptor; olfactory stimulus; physical property; predicting response; predictive modeling; rational number; receptor; receptor downregulation; recruit; relating to nervous system; 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.

摘要（项目1：气味空间的外围表示） 朝着了解嗅觉编码的进展受到了长期障碍的阻碍 刺激的性质和基本感觉生物学的复杂性。同时，描述 哺乳动物中的嗅觉编码将为多维刺激的独特窗口提供独特的窗口 由哺乳动物大脑代表。嗅觉系统使用大型气形受体家族来检测新的。 化学刺激的数量。必须克服更好地理解嗅觉的一个重要挑战是 确定系统代表嗅觉刺激的特征。正在做 因此，要求我们克服以前无法克服的技术挑战 大量接收器对大量气味的特异性，并且我们生成理论上 用于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 跨学科的努力，以全面的特征 体内的气形受体，并使用此信息明确，严格地测试了Odorint编码的新型模型。 该项目利用了嗅觉中的气压受体和肾小球之间的一对一对应关系 小鼠球。 AIM 1将表征大量受体（glomerulli）在清醒中的灵敏度 动物使用功能成像。 AIM 2将使用这些肾小球响应对特定接收器的使用 新兴的空间转录组学方法。 AIM 3将使用强大的基因组学测定法来识别 大量单个气味的最高亲和力受体。 AIM 4将测试一个新颖的理论框架 了解如何表示气味特征。这种大规模的体内多学科方法将提供 长期探索的数据和分析工具，以严格探索潜在的气味编码模型。