GLOMERULI AS FUNCTIONAL UNITS FOR OLFACTORY CODING

描述（改编自申请人的摘要）：主要嗅觉中心 在包括人类在内的各种动物的大脑中， 称为肾小球的突触模块阵列。这些中心被认为是 以化学拓扑方式组织，使得气味信息在空间上表示 但这一重要假设尚未得到验证 在一个提供解剖简单的优势的物种中， 可识别的肾小球、可接近的受体细胞和中枢神经元，以及 化学鉴定的，行为相关的气味此外，尽管戏剧性 尽管化学感觉研究取得了进展，但我们仍然不明白复杂的气味 刺激被编码在肾小球内和肾小球之间的神经活动中， 最终导致适当的行为反应。该项目建立在一个 坚实的技术经验和知识基础， 一个有利的模型，Manducasexta的嗅觉系统，这是可比的 在组织和功能上与脊椎动物相似， 肾小球趋化性假说的检验精度高于 在其他物种中是可能的。该模型系统还提供了一个特殊的 有机会解开内部和之间的突触神经回路 确定肾小球，以揭示特定的气味信息是如何 在大脑中的第一个中转站进行处理。通过细胞内 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，我们将专注于识别肾小球可识别 集群：（1）测试假设，肾小球组织 通过确定化学，时间和强度特性， 的行为显著气味刺激的分析和编码的个人 神经元支配特定肾小球;（2）表征突触回路 了解不同类型的神经元 与肾小球相互作用，形成输出信号 神经元投射到大脑的更高中心;（3）发展数学 特征神经元的模型，以生成关于其 生理学和突触相互作用。这项研究将促进了解 包括人类在内的所有动物的基本嗅觉机制， 为了有助于解释诸如嗅觉异常的感觉障碍， 嗅觉减退和嗅觉丧失。

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.