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: 10651870
• 负责人: Chih-Ying Su
• 金额: $ 23.7万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651870
• 关键词: 3-Dimensional; Affect; Afferent Neurons; Area; Characteristics; Cilia; Communities; Computer Models; Data Set; Dendrites; Detection; Disease; Disparity; 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; Neurons; Neurosciences; Odors; Olfactory Pathways; Olfactory Receptor Neurons; 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.

项目总结 本项目旨在描述已鉴定的嗅觉感受器神经元(Ons)的精确树突形态。 并用体积电子显微镜(EM)研究了树枝晶之间的结构-功能关系 形态和嗅觉敏感性。在神经系统中，信息是由专门的神经元接收的 称为树突的过程，其特征的树枝图案通常与特定的 神经元亚型的功能。例如，体感神经元的树枝状结构定义了几何形状 以及它们接受野的大小。相比之下，嗅觉感受器的大量纤毛或树突分支 神经元被认为可以增加感觉表面积，从而提高敏感度。然而，功能性的 树突的大小和形状对嗅觉的影响还没有实验确定。理解这一点 结构-功能关系因缺乏形态和形态计量学而受到特别阻碍 从确认身份的兽人那里得到的信息。为了弥合这一知识鸿沟，拟议的研究利用了强大的 黑腹金龟子的遗传工具包和易处理的嗅觉系统。苍蝇角的树突被包裹起来 在感觉性毛发中，称为感受器，分为四个形态类别：基本的，腔锥的，中间的 和毛状虫。为了准确定义ORN树枝状形态，我们取得了领先的技术突破， 使我们能够用冷冻固定的基因标记进行连续的块面扫描电子显微镜(SBEM) 触角组织。已识别神经元的3D重建显示出不同物种之间的显著形态差异 鸟儿被安置在不同的感受器班级中。基性和中性区的树枝状结构表现为多个 体腔锥形和毛状神经元的分支通常是不分支的。尽管神经元 表达相同的受体预计会表现出类似的树枝几何形状，我们发现 同型的基准角，表现出不同的分枝模式和不同的感觉表面积。是 某些ORN亚型的树枝分枝是否不同？如果是这样的话，这种形态的异质性是否会导致 对这些神经元群体中同型On之间的不同敏感性？此外，是气味检测 受不同ORN类型的分枝多样性和表面积差异的影响？这项提案将解决 这些基本问题是通过评估已确定的Orn的树突异质性(目标1)和通过 确定树突大小和形状对嗅觉敏感度的功能影响(目标2)。一个多学科的 方法-使用SBEM、分子遗传学和单感受器记录-将被采用。成功 这项提案的实施有望对树枝晶的大小和形状是否以及如何形成提供关键的见解 影响嗅觉功能。重要的是，识别出的Orns的大型形态和形态测量数据集 感觉树突将被生成并提供给神经科学界。这些丰富的信息 将促进比较形态计量分析和计算建模，并为未来铺平道路 研究确定不同ORN树枝状形态背后的分子机制。