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

Authors

Michelle N Bedenbaugh, Marie A Doyle, Caitlyn M Edwards, Nick Petersen, Dollada Srisai, Sydney H Hawkins, Nicholas T Low, Haley Mendoza-Romero, Jordan A Brown, Alexander S Vardy, Danny G Winder, Richard B Simerly

Published in

bioRxiv : the preprint server for biology. Feb 08, 2026. Epub Feb 08, 2026.

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.

PMID:
42745757
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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