Activation of 6-8-week-old new mature adult-born dentate granule cells contributes to anxiety-like behavior

Adult-born dentate granule cells (aDGCs) at 4-6 weeks of age are particularly excitable but subsequently develop the quiet properties of mature cells. Most existing studies have focused on the hyperactivity of 4-6-week-old aDGCs or neurogenesis, which confers stress resilience or buffers stress responses. However, the function of the quiet property of new mature aDGCs remains unclear. Here we used a retrovirus expressing cre recombinase in combination with an associated-adenovirus to specifically interfere with the activity of new mature aDGCs, and estimated anxiety-like behaviors by the open-field test and elevated plus maze test, antidepressant-like behaviors by the tail suspension test, and spatial memory by the Barnes maze test. We found that sustained hyperactivity of 6-8-week-old, but not 8-10-week-old, aDGCs induced anxiety-like behaviors, and suppression of the activity of 6-8-week-old aDGCs disturbed spatial memory. Meanwhile, sustained hyperactivity of 6-8-week-old aDGCs induced activation of mature dentate gyrus (DG) neurons and inhibition of immature aDGCs. Additionally, the mice showing anxiety-like behaviors induced by chronic mild immobilization stress exhibited increased activity in 6-8-week-old aDGCs. Furthermore, the sustained hyperactivity of mature DG neurons also induced anxiety-like behaviors and decreased the activity of immature aDGCs. Our results combined show that the excitation of 6-8-week-old new mature aDGCs, which prohibits them from normally entering the resting state, determines anxiety-like behavior, while the maintenance of normal excitation ability of 6-8-week-old new mature aDGCs confers memory. Our results suggests that strategies aimed at inhibiting unusual hyperactive new mature aDGCs at a restricted time window may protect against stress-related psychiatric disorders, such as anxiety and depression.