How a brain circuit controls the choice between fear and food

When faced with a potential threat, animals must instantly prioritize survival over everyday tasks such as searching for food. For a tiny mouse, standing in the middle of a wide-open, exposed area is terrifying; an instinct called thigmotaxis leads them to stick close to the safety of walls and perimeters. But how does the brain weigh this instinctual response against basic physical needs like hunger?

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Led by Dr. Benjamin Arenkiel, principal investigator at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s and Professor of Molecular and Human Genetics at Baylor, and published in Frontiers in Neuroscience, researchers at Texas Children's Hospital and Baylor College of Medicine (Baylor) have identified a specific neural pathway that acts as a central switchboard, highlighting the brain's decisive role in balancing survival instincts and basic needs.

Dr. Arenkiel and his team examined a cluster of brain cells in the bed nucleus of the stria terminalis (BNST), a region well known for processing stress and anxiety. Specifically, they focused on neurons that express corticotropin-releasing factor (CRF), a chemical messenger involved in the body's stress response.

Using real-time calcium imaging (fiber photometry) and light-driven genetic controls (optogenetics), the researchers observed and controlled these neurons in live mice during behavioral tests which yielded surprising results:

• Triggered by stress: Monitoring neural activity revealed that BNST CRF neurons are activated in response to a variety of stressors including open, exposed and novel environments.
• Driven to hide and fast: When the team artificially activated these CRF neurons, mice immediately sought out the safety of outer walls (avoidance behavior) and abruptly stopped eating (appetite suppression).
• The key wiring: By tracing where these neurons send signals, the team discovered that projections extending from the BNST directly to the lateral hypothalamus (LH), a main feeding center in the brain, controlled both the preference for safety and the suppression of appetite. In contrast, projections to other stress-related centers, such as the paraventricular nucleus (PVH), did not trigger these simultaneous shifts.

This discovery is significant because it offers new perspectives on how our brains manage stress and motivation, which could influence future treatments for psychiatric conditions like anxiety disorders. Dr. Arenkiel’s work also illuminates how we dynamically negotiate competing motivational states. By showing that a single pathway directly links threat-induced avoidance to appetite suppression, the study provides fresh insight into complex behavior.

Disorders like anxiety, post-traumatic stress disorder (PTSD), and eating disorders frequently overlap. Patients suffering from severe anxiety often experience sudden drops in appetite or, conversely, disrupted eating behaviors under stress. Target pathways, such as the BNST-to-LH circuit, offer potential avenues for future therapeutic interventions.

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Other contributors to this work include Juan Manuel Romero , Shae-Marie Stafford-Trujillo, Mitzy Mendoza, Pey-Shyuan Chin, Snigdha Srivastava, Mikhail Kochukov, Qingchun Tong. The authors are affiliated with one or more of the following institutions: Duncan NRI, Baylor College of Medicine, and University of Texas.

This work was supported in part by NIH grants P30DK144025, UM1HG006348, NIH R01 DK138518, and NIH R01 DK109934; USDA CRIS under grant 58-3092-5-008; and an NIH F31 Individual Predoctoral Fellowship (F31DK138784-01).