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

Press release

Monday February 12, 2024

An NIH-funded study in mice could shed light on treatments for psychiatric disorders linked to trauma and stress.

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 can 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 differentiate between witnessing another person’s reaction to a threat and 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 an observed threat experience are distinct from the patterns exhibited during a 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 .”

This study was supported by the intramural research programs of the NIAAA and the National Institute of Mental Health. Additional funding was provided through grants from the NIAAA and the National Institute of Neurological Disorders and Stroke.

About the National Institute on Alcohol Abuse and Alcoholism (NIAAA): The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the lead U.S. agency responsible for conducting and supporting research into the causes, consequences, prevention and treatment. of alcohol use disorders. NIAAA also disseminates its research findings to general, professional, and academic audiences. Additional information and publications on alcohol research are available at: https://www.niaaa.nih.gov.

About the National Institutes of Health (NIH):
The NIH, the nation’s medical research agency, consists of 27 institutes and centers and is part of the U.S. Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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