To determine whether the projection from the MS to the DG was involved in chronic stress‐induced depression, retrograde adeno‐associated virus expressing Cre‐recombinase driven by hSyn promoter (AAV‐hSyn‐Cre) was injected into the DG, and Cre‐dependent AAV encoding the clozapine‐N‐oxide (CNO)‐activated inhibitory designer receptors exclusively activated by designer drugs (DREADD), hM4Di (AAV‐DIO‐hM4Di‐mCherry),[16] was delivered into the MS (Figure1A–C), resulting in selective expression of hM4Di in DG‐projecting MS neurons. This evidence concerns the gene RIC8B and depressive disorder.