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

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 stress in one situation with behaviour during future stress.  

• Photo above: Bains Lab researchers, front row from left: lead researcher Núria Daviu, Toni-Lee Sterley, Neilen Resiah. Back row from left: David Rosenegger, Agnieszka Zurek, principal investigator Jaideep Bains, Tamás Füzesi. Not pictured are Dina Baimoukhametova and Govind Peringod. Photo by Adrian Shellard

Principal investigator Dr. Jaideep Bains, PhD, a professor in the Department of Physiology and Pharmacology and researcher at the CSM’s Hotchkiss Brain Institute (HBI), and his research team focused on the contributions of 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.

Escape to a shelter, or freeze in place

The research team used an experimental model in which mice are exposed to an expanding shadow above them to virtually mimic 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 that this group of neurons remembers past experience and uses this information to modify future behaviour. 

“If prior history of controllable stress makes individuals more resilient, even in different stressful situations, then it follows that one could train resilience by intentionally presenting controllable stressors,” notes lead researcher Dr. Núria Daviu, PhD, postdoctoral fellow in the Bains laboratory at the HBI.

Human experience mirrors findings

These findings are particularly intriguing considering that people behave similarly to the study subjects: people who have experienced a trauma during which they felt like they had no control often respond to subsequent stressors more passively, making it difficult to tackle challenges. Potentially, exposure to a stress over which the individual feels they have control could be an effective rehabilitation, or even preventive strategy, 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 the Hotchkiss Brain Institute, Brain and Mental Health is one of six research strategies guiding the University of Calgary in its Eyes High strategic direction. The strategy provides a unifying direction for brain and mental health research at the university and positions researchers to unlock new discoveries and treatments for brain health in our community.