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

Abstract

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.