GLOMERULI AS FUNCTIONAL UNITS FOR OLFACTORY CODING

肾小球作为嗅觉编码的功能单位

• 批准号: 6043367
• 负责人: JOHN G HILDEBRAND
• 金额: $ 22.93万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6043367
• 关键词: Manduca; afferent nerve; axon; chemoreceptors; confocal scanning microscopy; electrophysiology; gender difference; histochemistry /cytochemistry; innervation; neural information processing; neuroanatomy; neuropil; odors; olfactions; olfactory lobe; olfactory stimulus; pheromone; plant extracts; sensory discrimination; sensory mechanism; synapses; tobacco; voltage /patch clamp

An important challenge in olfactory research is to ascertain the functional significance of the synaptic glomeruli typically found in the first-order olfactory centers in vertebrate and invertebrate animals. Investigators have long sought to understand both the mapping of olfactory primary afferents onto the glomeruli and the nature of the sensory coding accomplished in those synaptic modules. A leading hypothesis is that the glomeruli are organized odotopically, with each glomerulus processing information about specific chemical features of odor molecules. This important hypothesis has not been tested comprehensively in a species offering the advantages of anatomical simplicity, identifiable glomeruli, accessible receptor cells and central neurons, and chemically identified, behaviorally relevant odors. This line of research is founded on a biologically compelling perspective: that relatively simple and experimentally favorable model systems offer unique opportunities for discovery and testing of principles of organization and function of neural systems, including those of human beings. The specific case of the olfactory system is especially persuasive. This project builds on a firm foundation of technical experience and knowledge about such a model, the olfactory system of the moth Manduca sexta, which has those advantages, is comparable to its vertebrate counterpart in organization and function, and permits the hypothesis of glomerular odotopy to be tested with greater precision than has been possible in other species. The proposed studies ask what attributes of odor molecules are analyzed and encoded by the olfactory system, how those features are mapped in "neural space" at the level of the glomerular array in the brain, and how the output neurons of individual glomeruli represent information about behaviorally relevant odors. This research will promote understanding of basic olfactory mechanisms in all animals, including mankind, and promises to contribute toward explanation and eventual treatment of sensory disorders such as parosmia, hyposmia, and anosmia. As specific aims, this proposal poses five questions: (1) how do the molecular receptive ranges and sensitivities of individual olfactory receptor cells vary among the various types discernible in the receptor epithelium; (2) what are the central projections of axons of individual, physiologically characterized types of olfactory receptor cells; (3) are there differences between the host-odor-processing olfactory receptor cells and glomeruli of males and females; (4) how are properties of specific, behaviorally significant odor molecules encoded by the principal output neurons of individual glomeruli; and (5) what are the molecular receptive ranges of individual, identified glomeruli, as reflected by their principal output neurons? Methods of intra- and extracellular and patch recording, intracellular staining, and confocal microscopy and computer-assisted image analysis and manipulation will be used to answer these questions. This will be the first study of the roles of individual, identified "ordinary" glomeruli and their input and output neurons in the central processing of specific, behaviorally significant odor molecules. It should add significantly to understanding of the analysis, coding, and discrimination of odors in the olfactory system.

嗅觉研究中的一个重要挑战是确定 突触肾小球的功能意义通常在 脊椎动物和无脊椎动物的一阶嗅觉中心。 长期以来，调查人员一直试图了解嗅觉的映射 主要传入肾小球和感觉编码的性质 在这些突触模块中完成。一个主要的假设是 肾小球是通过远程组织组织的，每个肾小球处理 有关气味分子的特定化学特征的信息。这 重要的假设尚未在物种中进行全面检验 提供解剖学简单性的优势，可识别的glomeruli， 可访问的受体细胞和中央神经元，化学鉴定， 行为相关的气味。 这一研究是基于生物学上令人信服的观点的： 那种相对简单且具有实验性的模型系统提供 发现和测试原理的独特机会 神经系统的组织和功能，包括人类的系统 生物。嗅觉系统的具体情况尤其是 有说服力。该项目以牢固的技术基础为基础 关于这种模型的经验和知识，即 具有这些优势的莫斯·曼达卡·塞克斯塔（Moth Manduca Sexta）与它的 脊椎动物在组织和功能中的对应物，并允许 肾小球那态的假设要高于比 在其他物种中可能是可能的。拟议的研究问什么 气味分子的属性由嗅觉分析和编码 系统，这些功能如何在“神经空间”中映射 大脑中的肾小球阵列，以及如何输出神经元 单个肾小球表示有关行为相关的信息 气味。 这项研究将促进对基本嗅觉的理解 包括人类在内的所有动物的机制，并承诺贡献 朝着解释和最终治疗感觉障碍（例如 帕罗森氏症，低质量和厌食症。 按照特定的目的，该提案提出了五个问题：（1） 单个嗅觉的分子接受范围和敏感性 受体细胞在受体中可分辨的各种类型中有所不同 上皮； （2）个体轴突的中心投影， 生理表征的嗅觉受体细胞类型； （3）是 宿主 - 偶像嗅觉受体之间存在差异 男性和女性的细胞和肾小球； （4）如何 特定的，行为意义的气味分子由主编码 单个肾小球的输出神经元； （5）什么是分子 个体的接受范围，被识别的肾小球，如 他们的主要输出神经元？ 细胞内和细胞外的方法 贴片记录，细胞内染色和共聚焦显微镜和 计算机辅助的图像分析和操纵将用于回答 这些问题。 这将是对个人角色的首次研究， “普通”肾小球及其中央的输入和输出神经元 处理特定的，行为重要的气味分子。 它 应该大大理解分析，编码和 嗅觉系统中气味的区分。