Adult neurogenesis in the mammalian olfactory bulb

描述（由申请人提供）：嗅球（OB）是CNS中仅有的两个部位之一，在该部位存在显著的纳塔尔后新神经元生成。大脑脑室下区（SVZ）的干细胞群每天产生超过30，000个新的神经祖细胞。这些细胞沿着称为吻侧迁移流（RMS）的结构迁移，最终到达OB，在OB中它们分化成抑制性中间神经元的两个主要群体中的一个并定居。超过一半的这些细胞将在到达OB后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扮演什么角色？它们在记忆中重要吗？它们是为了维持还是为了持续增长？我们将采用一种经典的策略来理解它们的功能：我们将摆脱它们，看看还缺少什么。使用选择性X射线照射室管膜下区，即这些细胞出生的区域，我们将暂时耗尽干细胞群体，减少新细胞流入嗅球。解剖学和生理学的一些测量将被用来确定神经发生的功能和重要性，以维持嗅球的正常功能。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回路中。它们会取代老细胞吗？它们只会取代其他新的细胞吗？它们会取代现有的突触还是形成全新的突触？面对这种强大的细胞替代，嗅觉是如何保持不变的？细胞更换的规则是什么？这些问题将结合系统水平生理学（多电极记录）和行为实验进行研究。了解神经元替代的动力学，以及同样重要的是，新细胞如何整合到现有的脑组织中，将对理解纳塔尔后神经发生及其可能的治疗控制产生重要影响。 公共卫生相关性神经发生，即成年人新神经元的增殖，是一种罕见的现象。嗅球细胞是仅有的两个发生这种情况的部位之一。了解这一过程，包括启动神经发生的因素以及新细胞整合到现有脑组织中的方式，将对疾病和脑损伤情况下的神经元替代产生影响。

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.