We’ve all felt the paralysing affects of danger or menace at some point in our lives.
Researchers at the University of Iowa have discovered the source of that threat reaction. A neural circuit connecting two unique brain regions, according to a recent study, determines how animals, including humans, respond to stressful conditions. The researchers utilised tests to show how rats reacted to threats passively or aggressively, and they linked each response to a specific neural pathway in the brain.
In another experiment, the researchers were successful in changing the brain circuit, leading rats to overcome what would have been a paralysing response to a threat and instead react aggressively.
The neural circuit identified with stress response connects the caudal medial prefrontal cortex to the midbrain dorsolateral periaqueductal grey. Clinching the connection, and how it regulates stress, is important, due to the known physical- and mental health impacts of chronic stress.
“A lot of chronic stress diseases like depression and anxiety disorders are associated with what we call a passive coping behaviour,” explains Jason Radley, 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.”
An important pathway controlling how animals react to stress is the caudal medial prefrontal cortex-midbrain dorsolateral periaqueductal grey, according to earlier studies. By deactivating the pathway and then observing how the rats reacted to a threat, Radley’s team was able to demonstrate the pathway’s significance. Rats could react in one of two ways: One is acting passively, which essentially means they did not react to the danger. The other is actively displaying a variety of behaviours, such as burying the danger (in the experiments, a shock probe), standing on its hind legs, or looking for a way out.
The scientists discovered that the rats responded passively, or without directly reacting to the threat when the stress neural circuit was deactivated.
“That shows this pathway is necessary for active coping behaviour,” Radley said.
By removing the bedding from the rats’ cages, which prevents them from attempting to bury the threat mechanism, the researchers next forced the rats to react passively. The rats changed their behaviour and actively reacted to the threat when the team activated the neural pathway. Even though the animals were left without their bedding, which should have prompted a passive response, the active reaction still took place. Additionally, blood tests performed before and after the activation of the rats’ neural circuits revealed that their levels of the stress hormone cortisol did not rise in the presence of the threat.
Stress hormones
“What that means is by activating the pathway, we saw broad stress-buffering effects,” Radley says. “It not only revived the rats’ active coping behaviours, but it also restored them and greatly decreased stress hormone release.”
In the third series of tests, the researchers exposed rats to chronic variable stress, which involved daily stress exposure over a period of two weeks. Following a two-week conditioning period, the rats were housed in cages and threatened. As the researchers had predicted, they responded in a passive, immobile manner, and their stress hormone levels increased.
According to Radley, humans experience chronic stress, which is why the chronic stress test is crucial.
Some people continue to carry these stress burdens for unknown reasons, which can result in physical and mental disorders. Others, however, exhibit little to no memory of the chronic stress in the past. This behaviour is known as “stress resilience” by researchers.
“It’s possible we can co-opt some of these brain circuits if we could understand the processes in the brain that can regulate resilience,” Radley said, though he adds this is not an imminent option.
The researchers plan to investigate the neural connections that are upstream and downstream of the caudal medial prefrontal cortex-midbrain dorsolateral periaqueductal grey pathway.
“We don’t understand how these effects are altering the brain more widely,” Radley said.
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