Targeting of sensory axons in the olfactory bulb

项目总结/摘要 这个建议的目的是了解嗅觉回路的第一个元素是如何正确连接的 在胚胎发育过程中。嗅觉神经元从嗅上皮投射轴突 大脑中的嗅球值得注意的是，从神经元延伸出来的轴突分散在 但选择表达相同的气味受体从一个大的受体库，汇聚 一起在灯泡内的特定可再现位置。这项研究计划解决了嗅觉如何 感觉轴突在大脑中找到正确的目标。该项目利用了相对简单的优势， 快速发展，并在实验中获得胚胎斑马鱼的感官指导研究 神经元在第一个目标中，我们将把气味受体的表达与灯泡内的目标位置联系起来。气味剂 受体参与嗅觉感觉轴突的指导，第二个目的是检查它们是否 在目标获取的初始阶段或稍后感觉轴突合并成 称为肾小球的独特神经纤毛结构。第三个目标涉及一个庞大而重要的阶级的作用 轴突导向线索，信号蛋白，在嗅觉轴突定位。这项工作将探讨如何指导 受体和嗅觉受体的表达是协调的，以及指导线索如何决定目标 感觉轴突在灯泡中的位置。嗅觉感觉神经元不断地诞生， 成熟的嗅球内的连接。了解这些连接在开发过程中如何形成 将是理解这一过程在神经退行性疾病中如何失败的关键。

PROJECT SUMMARY/ABSTRACT The objective of this proposal is to understand how the first elements of olfactory circuitry are correctly wired together during embryonic development. Odorant sensing neurons project axons from the olfactory epithelium to the olfactory bulb in the brain. Remarkably, axons extending from neurons that are scattered in the epithelium but choose to express the same odorant receptor from a large repertoire of receptors, converge together in specific reproducible locations within the bulb. This research proposal addresses how olfactory sensory axons locate their correct targets in the brain. The project takes advantage of the relative simplicity, rapid development, and experimental accessibility of the embryonic zebrafish to study the guidance of sensory neurons. In the first aim we will relate odorant receptor expression to target location within the bulb. Odorant receptors participate in the guidance of olfactory sensory axons and the second aim examines whether their contribution is important during the initial stages of target acquisition or later as sensory axons coalesce into distinct neuropilar structures called glomeruli. The third aim addresses the role of a large and important class of axonal guidance cues, the semaphorins, in olfactory axon targeting. This work will explore how guidance receptors and olfactory receptor expression is coordinated, and how guidance cues determine the target locations of sensory axons in the bulb. Olfactory sensory neurons are constantly being born and making new connections within the mature olfactory bulb. Understanding how these connections form during development will be essential in understanding how this process fails in neurodegenerative diseases.