Neurons in very few CNS populations continue to be produced during adulthood. The goal of our research is to understand the function of this adult neurogenesis by studying the regulation of neuronal precursor proliferation and survival in the dentate gyrus, a part of the hippocampal region in which large numbers of new neurons are born throughout adulthood. This year we completed an investigation of the naturally occurring death of newborn granule neurons in the adult dentate gyrus. Previous reports suggested that many of the newborn granule neurons disappear shortly after being born, but it was unclear whether this disappearance was actually due to cell death or simply to loss of the marker used to identify them. Additionally, it was unclear whether loss of cells continued until all new cells were gone, resulting in a fairly short lifespan for these neurons. Our work showed that nearly half of all the new granule cells in the adult dentate gyrus normally die within 4 weeks of being born. However, after this 4-week time point we saw no further death of the now mature granule neurons. This finding indicates that the cell death is likely to reflect a normal part of the development of new granule cells and suggests a competitive process through which neurons in functional or ?useful? circuits survive while cells that do not become integrated into functional circuits die. We compared the survival of newborn granule neurons in the adult rat to that of newborn granule neurons during the peak of dentate gyrus development during the first two postnatal weeks. We found that the survival rate of immature neurons was virtually identical in development and in adulthood. However, while the adult-born neurons stop dying after 4 weeks, those born in development continue to die at a slow but steady rate. This difference in late susceptibility of granule cells born at different times suggests that granule cells born during early postnatal development, when the rat has limited interaction with the environment may be preferentially replaced by neurons born in adulthood when the rat has more complex interaction with the environment and a fully-functional hippocampus.
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