Specific brain cells are critical for linking stress controllability and future behaviour – UCalgary News

Stress is ubiquitous, and at no time in recent memory has this been more evident than right now on a global scale. Our survival depends on our ability to continually adjust and respond to ever-evolving challenges in our world.

Interestingly, how we manage stress now has implications for how we will manage stress in the future. It is not necessarily about the actions we take now, but rather whether we feel our actions give us some control over the outcome during a difficult time. Psychologists and neuroscientists have pondered this stress control theory for decades, but how the brain intertwines the perception of controllability of one situation into decisions and actions for future situations has not been well understood.

Recent work by researchers at the Cumming School of Medicine (CSM),published in Nature Neuroscience, suggests an ancient population of cells in the brain that control stress hormones may hold the key to linking the controllability of stressin one situationwith behaviour during future stress.

Principal investigator Dr. Jaideep Bains, PhD, a professor in the Department of Physiology and Pharmacology and researcher at the CSMs Hotchkiss Brain Institute (HBI), and his research team focused onthe contributionsof corticotropin releasing hormone (CRH) neurons in the hypothalamus. The hypothalamus is a brain region that is instrumental in regulating autonomic bodily functions: things that are involuntary such as thirst, hunger, sleep, body temperature, blood pressure, and the release of stress hormones.

The research team used an experimental model in which mice are exposed to an expanding shadow above them tovirtuallymimic a predator approaching from the sky. They simultaneously monitored behaviour and recorded the activity of CRH neurons, and discovered that animals either escaped to a shelter, or froze in place.

The active/take-charge response, but not the freezing response, was preceded by an increase in the activity of CRH cells. Based on these findings, the researchers used light delivered via an optical fibre to selectively silence these cells. This use of light decreased escape behaviour and increased freezing behaviour, indicating that CRH neurons are key behavioural switches between passive and active reactions.

This was a very unexpected finding and is the first demonstration that these CRH cells, which control our automatic hormone response to stress, also play a permissive role in controlling survival behaviours

- Jaideep Bains

The team then took the study one step further to explore whether prior stressful experience with different levels of outcome control could alter CRH neuron activity and, by extension, the behaviour.Whether an individual had control or not of the outcome during stress had very different effects on these cells. Specifically, stress that was controlled in an earlier situation boosted the anticipatory activity of CRH neurons in the study, and this effect persisted in the looming shadow test, indicating thatthis group ofneuronsremembers past experience and uses this information to modify future behaviour.

Ifprior history of controllable stress makes individuals more resilient,even in different stressful situations,then it follows thatone could train resilienceby intentionally presentingcontrollable stressors, notes lead researcherDr. Nria Daviu, PhD, postdoctoral fellow in the Bains laboratory at the HBI.

These findings are particularly intriguing considering that people behave similarly to the study subjects: peoplewhohaveexperienced a trauma during which they felt like they had no control oftenrespond to subsequentstressorsmore passively, making it difficult to tackle challenges. Potentially, exposure toastressover which the individualfeels they have controlcould be an effective rehabilitation, or even preventivestrategy, for managing the effects of stress.

This research was funded by a Foundation grant from the Canadian Institutes for Health Research and support from the CSM Optogenetics and behaviour facility. Daviu is an Alberta Innovates Postdoctoral Fellow.

Led by theHotchkissBrainInstitute,BrainandMentalHealthis one of six research strategies guiding the University of Calgary in itsEyes Highstrategic direction. The strategy provides a unifying direction forbrainand mentalhealthresearch at the universityandpositions researchers to unlock new discoveriesandtreatments forbrainhealthin our community.

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Specific brain cells are critical for linking stress controllability and future behaviour - UCalgary News