GLOMERULI AS FUNCTIONAL UNITS FOR OLFACTORY CODING

描述(摘自申请者摘要)：初级嗅觉中枢 在包括人类在内的各种动物的大脑中，其特征是 称为肾小球的突触模块阵列。这些中心被认为是 化学组织的，使得气味信息在空间上表示 在肾小球中，但这一重要假设尚未得到检验 在一个物种中全面地提供了解剖简单的优势， 可识别的肾小球、可接近的受体细胞和中枢神经元，以及 化学鉴定，行为相关的气味。此外，尽管戏剧性的 化学感官研究的进展，我们仍然不知道复杂的气味是如何 刺激编码在神经活动中，在肾小球内和肾小球之间 最终导致适当的行为反应。这个项目建立在一个 扎实的技术经验和实验知识基础 良好的模型，水母的嗅觉系统，可与 它在组织和功能上与脊椎动物相对应，并允许 肾小球化疗假说将得到比以往更精确的检验 在其他物种中也是可能的。该型号系统还提供了一种特殊的 有机会解开内部和之间的突触神经回路 识别肾小球，以揭示气味信息的特异性 在大脑的第一个中转站被处理。通过细胞内的方式 记录和染色、细胞外多通道记录、激光扫描 共聚焦和透射电子显微镜，以及计算机辅助 数学建模，我们将重点研究可识别的肾小球 集群：(1)检验肾小球是有组织的这一假设 通过确定化学、时间和强度特性 的行为显著气味刺激由个体进行分析和编码 支配特定肾小球的神经元；(2)突触回路的特征 以了解肾小球内和肾小球之间各种类型的神经元是如何 与肾小球相关的相互作用形成输出所传达的信号 投射到大脑高级中枢的神经元；以及(3)发展数学 表征神经元的模型以生成关于其可测试的假设 生理学和突触相互作用。这项研究将促进理解 包括人类在内的所有动物的基本嗅觉机制，并承诺 有助于解释感觉障碍，如味觉障碍， 性欲减退和嗅觉障碍。

DESCRIPTION (adapted from applicant's abstract): The primary olfactory centers in the brains of diverse animals, including humans, are characterized by an array of synaptic modules called glomeruli. These centers are thought to be organized chemotopically, such that odor information is represented spatially among glomeruli, but 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. Moreover, despite dramatic advances in chemosensory research, we still do not understand how complex odor stimuli are encoded in neural activity, within and among glomeruli, that ultimately leads to appropriate behavioral responses. This project builds on a firm foundation of technical experience and knowledge about an experimentally favorable model, the olfactory system of Manduca sexta, which is comparable to its vertebrate counterpart in organization and function and permits the hypothesis of glomerular chemotopy to be tested with greater precision than has been possible in other species. This model system also offers an exceptional opportunity to unravel the synaptic neural circuitry within and between identified glomeruli in order to reveal how specific odor information is processed at its first way-station in the brain. By means of intracellular recording and staining, extracellular multichannel recording, laser-scanning confocal and transmission electron microscopy, and computer-assisted mathematical modeling, we will focus on identified glomeruli in recognizable clusters to: (1) test the hypothesis that glomeruli are organized chemotopically by determining what chemical, temporal, and intensity properties of behaviorally significant odor stimuli are analyzed and encoded by individual neurons innervating particular glomeruli; (2) characterize synaptic circuits within and between glomeruli to learn how the various types of neurons associated with glomeruli interact to shape the signas conveyed by output neurons projecting to higher centers in the brain; and (3) develop mathematical models of characterized neurons to generate testable hypotheses about their physiology and synaptic interactions. This research will promote understanding of basic olfactory mechanisms in all animals, including mankind, and promises to contribute toward explanation of sensory disorders such as parosmia, hyposmia, and anosmia.