The experiments proposed examine the control of cell proliferation and death in the developing olfactory system. The olfactory system has many desirable characteristics for studies of the mechanisms of neural maturation. It is highly organized, with clear lamination and a well-studied wiring diagram, facilitating quantitative examinations and making subtle alterations relatively ease to discern. Understanding cell proliferation is important because this fundamental step provides the neural and glial elements from which the brain in constructed. Understanding cell death is equally as important as it is the process that ultimately refines the connections made during early life. While the two processes are crucial for the formation of any neural region, they are especially important for an understanding of the organization of the olfactory system, as both olfactory receptor cells and central elements are constantly formed and lost throughout life. The proposed experiments examine cell proliferation and death in the olfactory mucosa, which contains the olfactory sensory cells, the olfactory bulb, which is the first-order processing station in the central nervous system, and the subventricular zone/rostral migratory stream, a region that supplies cells to the bulb. The specific questions we seek to answer include: 1) Olfactory mucosa: a) Since reduced function can decrease cell production, can enhanced activity increase it? b) How important is cell death during early development? Can it be regulated by activity as well? 2) Central Structures a) Can activity or chemical factors that regulate cell production in other areas affect the process here? b) Are there differences in the fate of cell born at different times during early life? c) Can these fates be manipulated by changing the functional state of the olfactory bulb?
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