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.

项目摘要 该项目旨在描述已识别的嗅觉受体神经元（ORNS）的精确树突形态 使用体积电子显微镜（EM）并研究树突状的结构 - 功能关系 形态和嗅觉敏感性。在神经系统中，专门神经元收到信息 所谓的树突的过程，其特征性树博模式通常与特定 神经元亚型的功能。例如，体感神经元的一克定义几何形状 和他们的接受场的大小。相反，嗅觉受体的众多纤毛或树突分支 神经元（ORN）被认为会增加感觉表面积以提高灵敏度。但是，功能 树突大小和形状对嗅觉的影响尚未实验定义。了解这一点 缺乏形态学和形态计量学尤其阻碍结构功能关系 来自确定的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 D. melanogaster的遗传工具包和可处理的嗅觉系统。飞鸟的树突被封装 在感官头发中，名为Sensora，属于四个形态学类别：基本，核心，中间 和trichoid。为了精确定义ORN树突形态，我们有开创性的技术突破 允许我们用冰冻的，遗传标记的连续块扫描电子显微镜（SBEM） 触角组织。鉴定神经元的3D重建揭示了显着的形态学多样性 ORNS属于不同的感觉式课程。基本和中间ORN的树突显示多个 分支，而腔内和trichoid神经​​元的分支通常没有分支。虽然神经元 预计表达相同的受体将展示相似的树皮几何形状，我们发现 同型基本ORN，而不是显示潜水员的分支模式和多样化的感觉表面积。是 对于某些ORN亚型的树突状树皮化多样化？如果是这样，这种形态异质性是否会产生 在这些神经元种群中同质ORN之间的敏感性可变？此外，是气味检测 受不同ORN类型的分支多样性和表面区域差异的影响？该建议将解决 这些基本问题通过评估已确定的ORN的树突异质性（AIM 1），以及通过 确定树突大小和形状对嗅觉灵敏度的功能影响（AIM 2）。多学科 方法 - 将使用SBEM，分子遗传学和单感应记录 - 将被使用。成功的 预计该提案的执行将产生有关树突大小和形状是否以及如何形状的关键见解 影响嗅觉功能。重要的是，针对确定的ORN的大型形态和形态学数据集 感官树突将被生成并提供给神经科学社区。这个丰富的信息 将促进比较形态计量学分析和计算建模，并为将来铺平道路 研究确定潜水员ORN树突形态的分子机制。