Mechanisms of Developmental Plasticity in the Mammalian Olfactory System

项目概要/摘要。 在哺乳动物的大脑中，嗅球是唯一一个不仅接受持续的 来自大脑的神经元祖细胞，但也来自嗅上皮的更新输入。嗅 感觉神经元（OSN）在动物的一生中不断再生。新生成的 OSN精确地投射到嗅球中的刻板位置，以维持感觉地图。已经 认为嗅觉系统由于其独特性， 持续再生能力。我们最近的研究结果表明，轴突靶向的OSN是敏感的， 在出生后第一周嗅觉发育过程中神经活动的剥夺和其他干扰， 提示OSN轴突靶向的关键时期。我们的数据进一步表明，两个独立的发展 在关键期之前和之后，计划是OSN精确定位的基础。开关 伴随着基因表达模式的显著变化。本申请的目的是 确定嗅觉系统发育关键期的分子调控。通过结合基因 操纵和转录组分析，我们已经开发出的方法，使我们能够直接比较， 出生后早期和成年期的发育计划。我们已经确定了候选基因 我们将测试它们在决定关键时期轴突动力学方面的作用， 确定关键期的时间。这些研究将提供轴突的机制见解 在OSN发育和成年神经发生期间的寻路。

Project Summary/Abstract. In the mammalian brain, the olfactory bulb is the only region that receives not only continuous infusion of neuronal progenitor cells from the brain, but also renewed input from the olfactory epithelium. The olfactory sensory neurons (OSNs) continuously regenerate throughout the life of the animal. The newly-generated OSNs project precisely to stereotypical positions in the olfactory bulb to maintain a sensory map. It has been thought that the olfactory system does not exhibit a critical period during development because of its unique, continuous regenerative capacity. Our recent results show that axonal targeting of the OSNs is sensitive to deprivation of neural activity and other perturbations during the first postnatal week in olfactory development, suggesting a critical period in OSN axon targeting. Our data further suggest that two separate developmental programs underlie the precise targeting of the OSNs before and after the critical period. The switch is accompanied by a prominent change in the patterns of gene expression. The objective of this application is to determine the molecular control of the critical period in olfactory system development. By combining genetic manipulation and transcriptome analyses, we have developed approaches that allow us to directly compare the developmental programs during early postnatal period and in adulthood. We have identified candidate genes and we will test their role in determining the axon dynamics during the critical period and their role in determining the timing of the critical period. These studies will provide mechanistic insights into axon pathfinding during OSN development and during adult neurogenesis.