RAPGEF4 and major depressive disorder: In the hippocampus, neuroanatomy and synaptic structures appear normal in mice deleted for Epac2 (Epac2-/-) or both Epac1 and Epac2 (Epac1/2-/-), but various molecular processes are affected leading to defect neurogenesis, deficits in long-term plasticity, spatial learning and social interactions, and increased anxiety and depression [19–21, 23].