Adult neurogenesis in the mammalian olfactory bulb

哺乳动物嗅球的成体神经发生

• 批准号: 8078857
• 负责人: Stuart J Firestein
• 金额: $ 31.84万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8078857
• 关键词: Ablation; Adult; Affect; Anatomy; Animals; Behavioral; Brain; Brain Injuries; Cell Count; Cell Death; Cell Survival; Cells; Chemicals; Code; Development; Disease; Electrodes; Environment; Future; Generations; Growth; Health; Homeostasis; Interneuron function; Interneurons; Laboratories; Maintenance; Measurement; Measures; Mediating; Memory; Morphology; Mus; Neurons; Odors; Output; Pathway interactions; Perception; Peripheral; Physiological; Physiology; Play; Population; Process; Property; Regulation; Resolution; Roentgen Rays; Role; Shapes; Signal Transduction; Site; Stem cells; Stream; Structure; Synapses; System; Testing; Therapeutic; Tissues; Travel; Work; adult neurogenesis; base; brain tissue; cell type; electrical property; extracellular; granule cell; irradiation; nerve stem cell; neural circuit; neurogenesis; neuronal replacement; olfactory bulb; progenitor; programs; research study; residence; stem cell population; subventricular zone

DESCRIPTION (provided by applicant): The olfactory bulb (OB) is one of only two sites in the CNS where there is significant post natal generation of new neurons. A population of stem cells in the Subventricular Zone (SVZ) of the brain gives rise to more than 30,000 new neural progenitor cells every day. These cells migrate along a structure known as the rostral migratory stream (RMS) eventually arriving at the OB where they differentiate into one of two major populations of inhibitory interneurons and take up residence. More than half of these cells will die within 2 weeks of arriving at the OB, suggesting that there is strong homeostatic regulation of the number of cells in the OB. What role do these new cells play in the function of the olfactory bulb? Are they important in memory? Are they for maintenance or for continued growth? We will pursue a classic strategy to understand their function: we will get rid of them and see what is missing. Using selective x- ray irradiation of the subventricular zone, the region where these cells are born, we will transiently deplete the population of stem cells and reduce the flow of new cells into the olfactory bulb. Several measurements of anatomy and physiology will be employed to determine the function and importance of neurogenesis for maintaining proper functioning in the olfactory bulb. A second question of importance is how these new cells integrate themselves into existing brain circuits. Do they displace older cells? Do they only replace other newer cells? Do they take over existing synapses or form entirely new ones? How does olfactory perception remain constant in the face of this robust cell replacement? What are the rules for cell replacement? These questions will be investigated with a combination of systems level physiology (multi electrode recordings) and behavioral experiments. Understanding the dynamics of neuronal replacement and, as importantly, how new cells can integrate into existing brain tissue, will have critical implications for understanding post natal neurogenesis and its possible control for therapeutic purposes. PUBLIC HEALTH RELEVANCE Neurogenesis, the proliferation of new neurons on the adult, is a rare occurrence. The cells of the olfactory bulb are one of only two sites where this occurs. Understanding this process, including the factors that initiate neurogenesis and the way new cells are integrated into existing brain tissue, will have implications for neuronal replacement in cases of disease and brain injury.

描述（由申请人提供）：嗅球（OB）是中枢神经系统中仅有的两个位点之一，那里有明显的新神经元后产生新的神经元。每天，大脑室室（SVZ）中的干细胞群每天可产生30,000多个新的神经祖细胞。这些细胞沿着称为延髓迁移流（RMS）的结构迁移，最终到达OB，它们分化为两个主要抑制性中间神经元的主要种群并占用居住。这些细胞中有一半以上会在到达OB后的2周内死亡，这表明OB中细胞数量的稳态调节很强。这些新细胞在嗅球的功能中起什么作用？它们在记忆中重要吗？它们是用于维护还是持续增长？我们将采取一种经典的策略来了解它们的功能：我们将摆脱它们，看看缺少什么。使用这些细胞诞生的区域的选择性X射线照射，我们将瞬时耗尽干细胞的种群，并减少新细胞的流入嗅球。将采用几种解剖学和生理学的测量，以确定神经发生在保持嗅球中适当功能的功能和重要性。第二个重要的问题是这些新细胞如何将自己整合到现有的大脑电路中。他们会取代较老的细胞吗？他们只取代其他较新的细胞吗？他们是否接管了现有的突触或形成全新的突触？面对这种健壮的细胞替代时，嗅觉如何保持恒定？更换细胞的规则是什么？这些问题将通过系统水平生理学（多电极记录）和行为实验的结合进行研究。了解神经元替代的动力学，并且重要的是，新细胞如何整合到现有的脑组织中，将对理解后神经发生及其可能用于治疗目的的控制具有关键意义。 公共卫生相关性神经发生，新神经元对成人的扩散是罕见的。嗅球的细胞是发生这种情况的仅有的两个位点之一。理解这一过程，包括启动神经发生的因素以及新细胞整合到现有的脑组织中的方式，将对疾病和脑损伤病例中的神经元替代产生影响。