In a new mouse study, researchers at the University of Iowa have traced where the reaction to a threat arises. The new study confirms a neural circuit linking two separate regions in the brain governs how animals, including humans, react to a stressful situation. The findings demonstrate how rats responded to a threat either passively or actively—and linked each reaction to a specific pathway in the brain.

The study, “Activity in a prefrontal-periaqueductal gray circuit overcomes behavioral and endocrine features of the passive coping stress response,” is published in the journal Proceedings of the National Academy of Sciences.

“A lot of chronic stress diseases like depression and anxiety disorders are associated with what we call a passive coping behavior,” explained Jason Radley, PhD, associate professor in the department of psychological and brain sciences and the study’s corresponding author. “We know that a lot of these conditions are caused by life stress. The simplest reason we’re interested in this pathway is thinking about it as a circuit that can promote resilience against stress.”

Previous research has identified the caudal medial prefrontal cortex-midbrain dorsolateral periaqueductal gray as a key pathway governing how animals respond to stress. Radley’s team confirmed the pathway’s importance by inactivating it, then observing how the rats responded to a threat.

The researchers observed that when they inactivated the rats’ stress neural circuit, the animals responded passively, meaning they did not directly respond to the threat.

The researchers plan to investigate the neutral connections that are upstream and downstream of the caudal medial prefrontal cortex-midbrain dorsolateral periaqueductal gray pathway.

“We don’t understand how these effects are altering the brain more widely,” Radley added. Their findings may pave the way to understanding the pathway and how it plays a role in stress-related diseases.

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