RAPGEF4 and Cognitive impairment: 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.