The Peripheral Representation of Odor Space

摘要(项目1：气味空间的外围表示法) 在理解嗅觉编码方面的进展一直受到以下因素造成的长期障碍的阻碍 刺激的性质和潜在感觉生物学的复杂性。同时，一种描述 在哺乳动物中的嗅觉编码将提供一个独特的窗口来了解多维刺激是如何 以哺乳动物的大脑为代表。嗅觉系统使用气味感受器大家族来检测巨大的 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 建立系统所代表的嗅觉刺激的特征的综合描述。vbl.做，做 因此，我们需要克服以前在确定刺激措施方面难以克服的技术挑战 大量受体对大量气味的特异性，我们产生了一种理论上的 量化和探索气味和感受器多维“空间”的框架。在这里，我们建议 一种跨学科的努力，以全面表征大量的气味反应特性 在体内的气味受体，并使用这些信息来明确和严格地测试气味编码的新模型。 这个项目利用气味感受器和嗅觉中的肾小球之间的一一对应。 一群老鼠。目标1将描述清醒、完整的大量受体(肾小球)的敏感性 使用功能成像的动物。Aim 2将这些肾小球反应映射到特定的受体上 新兴的空间转录学方法。AIM 3将使用一种强大的基于基因组学的分析来鉴定 对大量个体气味具有最高亲和力的受体。目标4将测试一个新的理论框架 了解气味特征是如何表现出来的。这种大规模的活体多学科方法将提供 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。

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.