Sex-specific control of feeding and defensive behaviors by MC3R neurons in the bed nuclei of the stria terminalis

ABSTRACT The bed nuclei of the stria terminalis (BST) is a nuclear complex that coordinates neuroendocrine, autonomic, and behavioral responses associated with maintaining homeostasis. Here, we demonstrate that melanocortin 3 receptor (MC3R) neurons in the BST (BST MC3R ) play a key role in modulating feeding behaviors and responses to stressful events. BST MC3R neurons are primarily GABAergic and colocalize with neuropeptides known to regulate feeding and affective behaviors. Chemogenetic activation of BST MC3R neurons causes reduced feeding, particularly in males. BST MC3R neurons are also robustly activated by stress and can control responses to stress and defensive behaviors in both sexes. Whole-brain monosynaptic rabies tracing identified multiple sexually dimorphic inputs to BST MC3R neurons that may contribute to observed functional sexual dimorphisms. Altogether, these data reveal that BST MC3R neurons participate in sexually dimorphic circuits that influence feeding and defensive behaviors, responses to stress, and may represent a potential therapeutic target for stress- and eating-related disorders.