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New research shows how the brain shifts into ‘stress mode’
By Emily Leighton
Researchers have identified a local brain circuit that helps regulate the body’s response to stress
By Emily Leighton
When we encounter a threat or challenge, the brain shifts our physiology into a different operating state.
Stress hormones rise. Blood pressure changes. The body moves from its everyday state to one of heightened readiness.
We’ve entered stress mode.
New research from Western University’s Schulich School of Medicine & Dentistry shows how the brain controls this shift. Researchers have identified a brain circuit that helps regulate the transition between states, offering new insight into how the body rapidly responds to stress and returns to normal.
Published in Cell Reports, the findings could provide a foundation for understanding stress-related disorders, including major depression and post-traumatic stress disorder.
"When we think about the stress response, it’s not simply on and off,” said Wataru Inoue, PhD, associate professor of physiology and pharmacology and senior author on the paper. “We’re changing how our fundamental physiology operates from a normal condition to an emergency condition.”
The study focused on a group of neurons in the hypothalamus, a region of the brain that helps regulate vital physiological functions, including hormone levels, body temperature and blood pressure.
Known as corticotropin-releasing hormone (CRH) neurons, these cells play a central role in the body’s hormonal stress response. They are active at low levels under normal conditions for housekeeping physiology, but shift to a high-activity state during stress for emergency readiness.
Inoue and his research team wanted to understand what controls that shift.
By combining recordings of neural activity in mouse models with computational modelling, the researchers identified a local feedback circuit that helps regulate CRH neuron activity.
Under normal circumstances, the circuit acts like a brake, keeping CRH neurons in a low-activity state. The researchers predict it may also act as a kind of gatekeeper, helping determine how sensitive those neurons are to potentially stressful signals arriving from other parts of the brain.
“The CRH neurons are not just listening to upstream brain areas telling them what to do,” Inoue said. “They have a local circuit that regulates their own activity.”
The researchers took an iterative approach with the study, moving back and forth between computational and experimental neuroscience by teaming up with Lyle Muller, PhD, adjunct professor in mathematics at Western, as well as researchers from the Krembil Institute and University of Calgary. They used patterns observed in mice to build models predicting how the circuit might work, then tested those predictions and used the results to refine their understanding.
For Inoue, their approach offers a more efficient way to tackle the complexity of the brain. Computational models can help researchers narrow the enormous number of possible neural connections to those most likely to matter, providing more focused questions to test in the lab.
The team is now building on the findings to study what happens to the circuit under chronic stress, including whether changes in how it operates are linked to dysregulation of the hormonal stress response, a hallmark of stress-related disorders.
"We really need to understand how the normal brain functions, and then how it becomes dysregulated,” he said. “That knowledge can provide an important path toward developing new diagnostic tools, interventions or treatments.”