Behavioral consequences of increasing adult hippocampal neurogenesis

The hippocampus is a brain structure involved in memory as well as anxiety and depression-related behavior. One unique property of the hippocampus is that adult neurogenesis occurs in this region. Rodent studies in which adult hippocampal neurogenesis is ablated have shown a role for this process in the cognitive domain, specifically in pattern separation tasks, as well as in mediating the behavioral effects of antidepressants. These studies have furnished the intriguing hypothesis that increasing adult hippocampal neurogenesis may improve these functions and therefore serve as a target for novel treatments for cognitive impairments as well as depression and anxiety disorders. Here, we use both genetic and pharmacological models to increase adult neurogenesis in mice. Under baseline conditions, we find that increasing adult hippocampal neurogenesis is sufficient to improve performance in a fear-based pattern separation task, but has no effect on exploratory, anxiety or depression-related behavior. In mice exposed to voluntary exercise, increasing adult hippocampal neurogenesis increases exploration, without affecting anxiety or depression-related behavior. Finally, in mice treated with chronic corticosterone, a model of anxiety and depression, increasing adult hippocampal neurogenesis is sufficient to prevent the behavioral effect of CORT on anxiety and depression-related behavior. Here, we therefore describe dissociations between the effects of increasing adult hippocampal neurogenesis under baseline, voluntary exercise and chronic stress conditions. Together, our results suggest that increasing adult hippocampal neurogenesis has therapeutic potential for both cognitive, and anxiety and depression-related disorders.