Our circuit-level analysis identified the LS-A2AR+ → DMH and LS-A2AR+ → LHb pathways as the main downstream target for top-down control of depressive-like behavior by LS-A2AR. The DMH is a main output of the LS, establishing a feedback loop to control LS circuits through peptidergic signals such as CRF and vasopressin, which is proposed to be involved in depression, fear and anxiety (reviewed in22,24). This evidence concerns the gene CRH and depressive disorder.