GLOMERULI AS FUNCTIONAL UNITS FOR OLFACTORY CODING

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发现在 脊椎动物和无脊椎动物的一级嗅觉中心。 长期以来，研究人员一直试图了解嗅觉的映射， 初级传入到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， 肾小球的组织是odotopically，每个肾小球处理 气味分子的特定化学特征的信息。这 一个重要的假设还没有在一个物种中得到全面的检验 提供解剖简单，可识别肾小球， 可接近的受体细胞和中枢神经元，并经化学鉴定， 行为相关的气味。 这一系列研究是建立在生物学上令人信服的观点上的： 相对简单和实验上有利的模型系统提供了 独特的机会，发现和测试的原则， 神经系统的组织和功能，包括人类的神经系统 生物。嗅觉系统的具体情况尤其是 很有说服力该项目建立在坚实的技术基础上， 关于这种模型的经验和知识， 蛾Manduca sexta，具有这些优势，可与其 脊椎动物的组织和功能，并允许 肾小球异位假说的检验精度高于 在其他物种中是可能的。这些研究提出的问题是， 气味分子的属性由嗅觉系统分析和编码， 系统，这些特征是如何在“神经空间”中映射的， 大脑中的肾小球阵列，以及输出神经元如何 单个肾小球代表了行为相关的信息， 气味 这一研究将促进对嗅觉基础的理解 包括人类在内的所有动物的机制，并承诺 解释和最终治疗感觉障碍， 嗅觉异常、嗅觉减退和嗅觉丧失。 作为具体目标，该建议提出了五个问题：（1）如何 个体嗅觉的分子感受范围和敏感性 受体细胞在受体中可辨别的各种类型之间变化 上皮细胞;（2）个体轴突的中心投射是什么， 生理学特征类型的嗅觉受体细胞;（3）是 宿主处理气味的嗅觉受体 细胞和肾小球的男性和女性;（4）如何属性 特定的，行为上重要的气味分子编码的主要 单个肾小球的输出神经元;和（5）什么是分子 个体的接受范围，确定肾小球，如 它们的主要输出神经元 细胞内和细胞外的方法， 斑片记录、细胞内染色和共聚焦显微镜， 计算机辅助图像分析和处理将被用来回答 这些问题。 这将是第一次研究个人的作用， “普通”肾小球及其中枢的输入和输出神经元 处理特定的、行为上显著的气味分子。 它 应该大大增加对分析、编码和 嗅觉系统对气味的辨别。

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.