In conclusion, we showed that (1) Epac2 had a dominant role in emotional cognitive function and mood control over Epac1; (2) impaired hippocampal neurogenesis was among the most important factors that related to anxiety, depressive-like behaviors and fear-related cognitive deficits in Epac2-deficient mice; (3) the neurogenesis deficit might be attributed to the indispensable role of Epac2 downstream to GABAergic regulation of recruiting quiescent cells to the active proliferative cell pool. The gene discussed is RAPGEF4; the disease is Anxiety.