UC San Diego

This work explores the functional role of adult hippocampal neurogenesis in the context of dentate gyrus (DG) and hippocampal function as well as in the context of long term dysfunction characteristic of the degenerative brain. To probe the role of adult hippocampal neurogenesis in pattern separation function, two behavioral tasks have been developed and applied to models in which neurogenesis has been artificially ablated or reduced, increased by environmental stimulation, and impaired long term in the diseased brain. The work presented in this thesis provides evidence for a functional role of adult hippocampal neurogenesis in spatial discrimination consistent with a role in spatial pattern separation, a function that does not appear to be modulated by environmental enrichment. Despite the well known correlations between increased rate of neurogenesis and performance on learning and memory tasks, modulating the number of mature dentate granule cells, without increasing the pool of immature neurons stably over time, does not appear to affect spatial discrimination behavior. However, long term deficits in adult neurogenesis, as examined in a rodent model of the neurodegenerative disease Huntington's, may contribute to deficits in spatial discrimination observed in R6 mice expressing the mutant human huntingtin transgene. Further investigation into the mechanism(s) underlying the role of adult neurogenesis in spatial pattern separation would both provide insight into the biological process of neurogenesis in the adult brain and contribute to our understanding of cognition in the context of the normal and diseased brain.