Adult neurogenesis in the mammalian olfactory bulb

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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.