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