Mechanisms of Developmental Plasticity in the Mammalian Olfactory System

哺乳动物嗅觉系统发育可塑性机制

• 批准号: 10174905
• 负责人: Congrong Ron Yu
• 金额: $ 47.27万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10174905
• 关键词: Adult; Affect; Aging; Alzheimer' s Disease; Animals; Axon; Behavior; Birth; Brain; Candidate Disease Gene; Continuous Infusion; Data; Development; Developmental Process; Embryo; Failure; Gene Expression Profile; Genes; Genetic; Goals; Growth; Impairment; Knowledge; Label; Lead; Life; Maps; Molecular; Motivation; Mus; Natural regeneration; Nerve Regeneration; Nervous System Physiology; Nervous system structure; Neurodegenerative Disorders; Neurons; Olfactory Epithelium; Olfactory Pathways; Parkinson Disease; Pathologic; Pattern; Perinatal; Play; Positioning Attribute; Process; Quality of life; Regenerative Medicine; Regenerative capacity; Regulation; Role; Sensory; Structure; System; Systems Development; Testing; WNT Signaling Pathway; adult neurogenesis; axonal pathfinding; brain cell; critical period; deprivation; developmental plasticity; experimental study; functional restoration; genetic manipulation; genetic testing; innovation; insight; loss of function; mature animal; nerve stem cell; neurodevelopment; neuron development; novel; novel strategies; olfactory bulb; olfactory sensory neurons; postnatal; postnatal development; postnatal period; preventive intervention; programs; public health relevance; receptor; regenerative repair; relating to nervous system; repaired; scaffold; sensory system; single-cell RNA sequencing; transcriptome

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.

项目摘要/摘要。 在哺乳动物的大脑中，嗅球是唯一接收连续输注的区域 来自大脑的神经元祖细胞，但也从嗅觉上皮重新输入。嗅觉 感觉神经元（OSN）在动物的整个生命中不断再生。新生成的 OSNS精确地将嗅觉灯泡中的刻板位置投影以维持感觉图。它一直 认为嗅觉系统在开发过程中没有出现关键时期，因为它具有独特的， 连续再生能力。我们最近的结果表明，OSN的轴突靶向对 在嗅觉开发的第一个周后，神经活动和其他扰动的剥夺， 建议在OSN轴突靶向中存在关键时期。我们的数据进一步表明两个单独的发展 在关键时期之前和之后的OSN的确切靶向基础。开关是 伴随着基因表达模式的显着变化。该应用的目的是 确定嗅觉系统开发中关键时期的分子控制。通过结合遗传 操纵和转录组分析，我们开发了方法，使我们能够直接比较 在产后和成年期间的发展计划。我们已经确定了候选基因 我们将测试他们在关键时期确定轴突动态及其在其中的作用的作用 确定关键时期的时间。这些研究将提供对轴突的机械见解 在OSN发育和成年神经发生过程中进行探路。