Researchers identify brain center playing key role in learned response to direct and indirect threats

Scientists have identified an area in the brain’s frontal cortex that can coordinate an animal’s response to potentially traumatic situations. Understanding where and how neural circuits involving the frontal cortex regulate these functions, and how these circuits might malfunction, may provide insight into their role in trauma- and stress-related psychiatric disorders in humans. The study, led by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, was published in Nature.

“Experiencing traumatic events is often the cause of trauma- and stress-related psychiatric disorders, including alcohol use disorders (AUD),” said study lead author Andrew Holmes. , Ph.D., principal investigator at the NIAAA Behavioral Laboratory. and genomic neuroscience. “Additionally, seeing other people experience traumatic events may also contribute to these disorders.”

In animal models of stress and trauma, learning about potential sources of threat by observing how others handle danger can be an effective way to avoid harm. Understanding differences in how the brain processes the direct experience of threat versus observing another’s response to threat may shed light on the factors that predispose humans to trauma-related psychiatric disorders and stress.

The scientists examined the brain activity of mice subjected to observational fear learning, a process by which animals discover sources of danger and minimize their own risks by observing how others react to threats. The researchers focused on the dorsomedial prefrontal cortex (dmPFC), a brain area known to play a key role in processing social information and interpreting threats in mice, humans and other animals.

The researchers measured activity in neural pathways leading to and away from the dmPFC in mice who observed other mice learning to associate a sound signal with a mild foot shock. Animals that receive this signal-shock signal typically learn to “freeze” or become still when they hear the sound signal.

The scientists then presented observing mice with the sound-shock-foot pairing and measured activity in the same dmPFC neuronal pathways. They found that when observer mice faced the “threat” of the sound signal, they exhibited coordinated recruitment and calibration of pathways that mobilize or suppress the freezing response.

“It remains unclear whether there are brain mechanisms that distinguish witnessing another’s response to threat from directly experiencing that threat,” says Dr. Holmes. “However, our study revealed that dmPFC pathways are necessary for mice to learn threats through observation, and that the activity patterns exhibited by dmPFC neurons during observed threat experience are distinct from the patterns exhibited during the direct threat experience.”

The researchers suspect that a critical function of the dmPFC in bystander mice may be to balance the need to minimize damage (i.e. freezing) with the need to perform other essential survival functions (i.e. example, assessing risk or comforting others). They also say the findings suggest that maladaptive responses to socially learned threats may result in part from deficits in dmPFC pathways and may indicate a potential role for dmPFC deficits in trauma- and stress-related psychiatric disorders in humans. .

“This study highlights the importance of basic neurobehavioral research in defining the neurocircuitry that contributes to elements of post-traumatic stress, a key contributor to psychiatric disorders and alcohol use disorders in particular,” said Dr. NIAAA Director, Dr. George F. Koob. “By identifying the patterns of brain activity that underlie how animals learn threats from others, these findings could potentially inform prevention and treatment approaches for AUD and other stress/trauma-related disorders .”