Adult neurogenesis in the mammalian olfactory bulb

描述（由申请人提供）：嗅球（OB）是中枢神经系统中仅有的两个有重要的出生后新神经元生成的部位之一。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。这些细胞沿着一个被称为吻侧迁移流（RMS）的结构迁移，最终到达OB，在那里它们分化成两个主要的抑制性中间神经元群体之一并定居下来。这些细胞中有一半以上会在到达嗅球后的两周内死亡，这表明嗅球中细胞的数量有很强的稳态调节。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，看看缺失了什么。使用选择性的x射线照射脑室下区，也就是这些细胞诞生的区域，我们将短暂地耗尽干细胞的数量，减少新细胞流入嗅球。一些解剖学和生理学的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？它们只会替换其他新的细胞吗？它们是接管现有的突触还是形成全新的突触？面对这种强大的细胞替换，嗅觉感知是如何保持不变的？细胞替换的规则是什么？这些问题将结合系统水平生理学（多电极记录）和行为实验进行调查。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，将对理解出生后神经发生及其可能的治疗控制具有重要意义。神经发生，即新神经元在成人身上的增殖，是一种罕见的现象。嗅球细胞是发生这种情况的仅有的两个部位之一。了解这一过程，包括启动神经发生的因素和新细胞融入现有脑组织的方式，将对疾病和脑损伤病例中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.