In a new study, researchers found that learned fear responses enable animals—including humans—to flee or freeze in the face of a perceived threat.
But if these behaviors persist after the danger lifts, they can become paralyzing and disabling. That’s a key element of post-traumatic stress disorder (PTSD).
The research was conducted by a team at Vanderbilt University Medical Center.
To explore how fear becomes entrenched, the researchers examined the precise neuronal pathways in the brains of mice that trigger fear responses, and which normally extinguish the behaviors once the danger has passed.
This study challenges conventional wisdom about how the brain is “remodeled” in response to the intrusion—and subsequent removal—of fear-inducing stimuli.
It’s widely assumed that the brain’s advanced seat of cognition, the cerebral cortex, decides how to respond to a threat and its order “filters down” to a more primitive part of the brain, the central amygdala, where the flee-or-freeze response is executed and terminated.
But the team found something unexpected: initiation and termination of learned freezing responses occur in cortical parts of the amygdala via a flexible remodeling of excitation onto two distinct subtypes of central amygdala “output channels.”
It is here that the animal learns to fear certain stimuli through one neuronal channel and “unlearns” the fear through the other channel once the threat is gone.
According to the team, people who have been exposed to stress or trauma can form associations between environmental cues and the fear that their lives are in danger.
If the association persists after the threat is gone and the environmental cues continue to trigger anxiety and fear, that can lead to PTSD.
Currently, PTSD is treated by gradually exposing patients to the environmental cues that trigger their fear responses to help their brains “re-learn” to extinguish the behaviors.
But exposure therapy is intense. Some patients can’t tolerate the anxiety it can cause.
The next step for the researchers is to look for receptors or proteins expressed by cells in one channel but not in the other.
The knowledge gained about the fear response may advance understanding of other brain disorders including drug and alcohol abuse.
The lead author of the study is Sachin Patel, MD, Ph.D., the director of the Division of General Psychiatry at Vanderbilt.
The study is published in Nature Neuroscience.
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