HMN 2025: How Brain cells controlling stress switch on and off in hourly cycles

University of Otago ?t?kou Whakaihu Waka-led research has found stress-controlling brain cells switch on and off in a steady rhythm about once every hour—even when nothing stressful is happening.

Senior author Associate Professor Karl Iremonger, of Otago’s Department of Physiology and Center for Neuroendocrinology, says these rhythms shape activity patterns and alertness.

“These bursts of brain cell activity seem to act like a natural ‘wake-up’ signal, and often lead to a rise in stress hormones, or cortisol.

“This world-first research opens the door to exploring how these patterns affect health, mood, and sleep,” he says.

For the study, published in PNAS, the researchers used an optical technique called photometry to track brain cell activity of mice and rats.

“This involved shining light into the animals’ brains, allowing us to monitor brain cell activity over the day and night as the animals moved around freely. We could then look at how the activity of brain pathways is coordinated with sleep/wake patterns and stress hormone levels.”

A group of brain cells called corticotropin-releasing hormone (CRH) neurons were found to be particularly important for the daily rhythms of stress hormone release.

“These neurons turn on and off in a regular pattern about once every hour. Interestingly, we found that these changes were coordinated with patterns of sleep and waking, which suggests that the pattern of release is coordinated with wakefulness or alertness.

“We also found when the CRH neurons were artificially activated, this changed the animals’ behavior—animals that were previously quietly resting became hyper-active.”

Associate Professor Iremonger says the research findings may lead to a better understanding of how disrupted stress rhythms can result in changes in mood and disrupted sleep.

Drugs that decrease CRH stress neuron activity may also be beneficial at treating conditions associated with hyper-active stress responses.

“Our new research is helping us to understand how the brain controls these normal rhythms of stress hormone release. Knowing how these brain signals work will help us understand the links between stress hormone levels, alertness and mental health.”