Corticotropin-releasing factor neurons in the bed nucleus of the stria terminalis modulate avoidance behaviors and feeding

Introduction Animals rely on defensive avoidance of exposed or potentially threatening environments as a fundamental survival strategy, often expressing this behavior as thigmotaxis, or a preference for the periphery of an open space. However, researchers still do not understand how neural circuits coordinate avoidance behavior with competing physiological drives such as feeding. In this study, we investigate how corticotropin-releasing factor (CRF)-expressing neurons in the bed nucleus of the stria terminalis (BNST) integrate environmental avoidance and feeding behavior. Methods We used adult male and female mice and applied fiber photometry to monitor BNST CRF neuronal activity in vivo. We performed both acute and chronic manipulations of these neurons to test their causal role in behavior. We used behavioral assays to measure avoidance (thigmotaxis) and food intake. We also conducted anatomical tracing to identify projections from BNST CRF neurons to hypothalamic regions and used axon terminal optogenetic stimulation to test the functional contributions of specific pathways. Results BNST CRF neurons increased their activity in response to diverse stressors. When we activated these neurons, mice showed increased periphery-oriented behavior and reduced food intake. Anatomical tracing revealed that BNST CRF neurons project to key hypothalamic regions, including the lateral hypothalamus (LH) and paraventricular hypothalamic nucleus (PVH). When we stimulated BNST CRF→LH projections, we observed both increased avoidance behavior and suppressed feeding. In contrast, stimulating BNST CRF→PVH projections did not significantly alter either behavior. Discussion Our findings identify BNST CRF neurons as a circuit node that integrates stress and feeding-related signals to bias behavioral output. Specifically, BNST CRF projections to the LH drive the coupling of avoidance and feeding suppression. These results provide new insight into how the brain coordinates competing motivational states such as avoidance and feeding.