Analysis of sensory dendrite morphology and its impact on olfactory sensitivity

感觉树突形态分析及其对嗅觉敏感度的影响

• 批准号: 10510403
• 负责人: Chih-Ying Su
• 金额: $ 19.75万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10510403
• 关键词: 3-Dimensional; Address; Affect; Afferent Neurons; Area; Characteristics; Cilia; Communities; Computer Models; Data Set; Dendrites; Detection; Disease; Dose; Drosophila genus; Electron Microscopy; Encapsulated; Exhibits; Face; Future; Genetic; Geometry; Heterogeneity; Insecta; Knowledge; Label; Lead; Length; Malaria; Mediating; Modeling; Molecular; Molecular Genetics; Morphology; Names; Nervous system structure; Neurons; Neurosciences; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Olfactory tract; Pattern; Population; Process; Research; Sample Size; Scanning Electron Microscopy; Sensory; Sensory Hair; Shapes; Smell Perception; Structure-Activity Relationship; Surface; Testing; Tissues; comparative; falls; fly; improved; insect disease vector; insight; interdisciplinary approach; receptive field; receptor; reconstruction; response; somatosensory; three-dimensional modeling

PROJECT SUMMARY This project aims to describe the precise dendritic morphology of identified olfactory receptor neurons (ORNs) with volume electron microscopy (EM) and to investigate the structure-function relationship between dendritic morphology and olfactory sensitivity. In the nervous system, information is received by specialized neuronal processes termed dendrites, whose characteristic arborization patterns are typically associated with specific functions of neuronal subtypes. For example, the arborizations of somatosensory neurons define the geometry and size of their receptive fields. In contrast, the numerous cilia or dendritic branches of olfactory receptor neurons (ORNs) are thought to increase sensory surface area for heightened sensitivity. However, the functional impacts of dendritic size and shape on olfaction have yet to be experimentally defined. Understanding this structure-function relationship has been particularly hindered by the lack of morphological and morphometric information from identified ORNs. To bridge this knowledge gap, the proposed research leverages the powerful genetic toolkit and tractable olfactory system of D. melanogaster. The dendrites of fly ORNs are encapsulated in sensory hairs, named sensilla, which fall into four morphological classes: basiconic, coeloconic, intermediate and trichoid. To precisely define ORN dendritic morphologies, we have pioneered technical breakthroughs which allowed us to perform serial block-face scanning electron microscopy (SBEM) with cryofixed, genetically labeled antennal tissues. 3D reconstructions of identified neurons reveal remarkable morphological diversity among ORNs housed in different sensillum classes. The dendrites of basiconic and intermediate ORNs display multiple branches, whereas those of coeloconic and trichoid neurons are typically unbranched. And although neurons expressing the same receptor are expected to exhibit similar arborization geometry, we found subsets of homotypic basiconic ORNs which instead show diverse branching patterns and varied sensory surface area. Is dendritic arborization diverse for certain ORN subtypes? If so, does this morphological heterogeneity give rise to variable sensitivity among homotypic ORNs in these neuronal populations? Moreover, is odor detection affected by the branching diversity and surface-area disparity of different ORN types? This proposal will address these fundamental questions by evaluating the dendritic heterogeneity of identified ORNs (Aim 1), and by determining the functional impact of dendritic size and shape on olfactory sensitivity (Aim 2). A multidisciplinary approach—employing SBEM, molecular genetics, and single-sensillum recording—will be employed. Successful execution of this proposal is expected to yield critical insights into whether and how dendritic size and shape impact olfactory function. Importantly, a large morphological and morphometric dataset for identified ORNs’ sensory dendrites will be generated and made available to the neuroscience community. This rich information will facilitate comparative morphometric analyses and computational modeling, and also pave the way for future studies to determine the molecular mechanisms underlying diverse ORN dendritic morphologies.

项目概要 该项目旨在描述已识别的嗅觉受体神经元（ORN）的精确树突形态 体积电子显微镜（EM）并研究树突之间的结构与功能关系 形态和嗅觉敏感性。在神经系统中，信息由专门的神经元接收 称为树突的过程，其特征性的树枝化模式通常与特定的 神经元亚型的功能。例如，体感神经元的树状结构定义了几何形状 以及它们的感受野的大小。相反，嗅觉受体的大量纤毛或树突分支 神经元（ORN）被认为可以增加感觉表面积以提高敏感性。然而，功能性 树突大小和形状对嗅觉的影响尚未通过实验确定。了解这一点 由于缺乏形态学和形态计量学，结构-功能关系受到特别阻碍。 来自已识别 ORN 的信息。为了弥合这一知识差距，拟议的研究利用了强大的 黑腹果蝇的遗传工具包和易处理的嗅觉系统。果蝇 ORN 的树突被封装 感觉毛中的感觉毛，称为感器，分为四个形态类别：基础毛、腔毛、中间毛 和毛状。为了精确定义 ORN 树突形态，我们率先取得了技术突破， 使我们能够使用冷冻固定、基因标记的序列块面扫描电子显微镜 (SBEM) 触角组织。已识别神经元的 3D 重建揭示了神经元之间显着的形态多样性 ORN 位于不同的感器类别中。基本和中间 ORN 的树突显示出多个 分支，而腔室和毛样神经元的分支通常是无分支的。尽管神经元 表达相同受体预计会表现出相似的树枝化几何形状，我们发现了 相反，同型基本 ORN 表现出不同的分支模式和不同的感觉表面积。是 某些 ORN 亚型的树突分枝是否不同？如果是这样，这种形态异质性是否会导致 对这些神经元群体中同型 ORN 的可变敏感性？另外，就是气味检测 受不同 ORN 类型的分支多样性和表面积差异的影响吗？该提案将解决 通过评估已识别的 ORN 的树突异质性（目标 1），并通过 确定树突大小和形状对嗅觉敏感性的功能影响（目标 2）。多学科 将采用SBEM、分子遗传学和单感器记录的方法。成功的 该提案的执行预计将产生关于树突大小和形状是否以及如何的重要见解 影响嗅觉功能。重要的是，已识别的 ORN 的大型形态学和形态测量数据集 感觉树突将被生成并提供给神经科学界。这丰富的信息 将促进比较形态测量分析和计算建模，并为未来铺平道路 研究以确定不同 ORN 树突形态背后的分子机制。