This project focuses on the interactions between experience and adult neurogenesis in the hippocampal region of the brain. We are interested in understanding how experiences, including learning and stressful experiences, regulate adult neurogenesis and how the new neurons alter responses in these situations. We study the regulation and function of adult neurogenesis in rats and mice, which show continued production of new neurons throughout adulthood similar to that in primates, including humans. We have previously found that specifically inhibiting adult neurogenesis in mice increases their hormonal and behavioral responses to stress, increasing depressive-like behavior. During the past year, we have focused on identifying structural and behavioral changes that occur when adult neurogenesis is inhibited using pharmacogenetic manipulations in mice or rats. To do this, we used transgenic rat and mouse lines that we developed that allow us to stop neurogenesis with no side effects by feeding the animals an antiviral drug. We found that loss of new neurons affects fear and anxiety-like responses in mice that have experienced mild footshock only if the shock was ambiguously cued, or somewhat unpredictable. If mice experienced the same shock but with a cue that predicted exactly when the shock would come, the loss of new neurons had no effect on future behavior. Unpredictability is a key feature of stressors, suggesting that adult neurogenesis may alter response to stress because of its ambiguity. These findings also have implications for learning, because solutions to difficult tasks are often more ambiguous than solutions to simple tasks. We also found that inhibition of adult neurogensis in our transgenic rats alters the structure of the hippocampus, decreasing the volume of the dentate gyrus and CA3 portions of the hippocampus. Decreased hippocampal volume also occurred after chronic unpredictable stress, but the effects of stress were faster and more widespread, suggesting that decreased adult neurogenesis is not responsible for the hippocampal volume loss caused by stress and, by extension, depressive illness.
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