Brain Mechanism That Regulates Fear Discovered in Mice, Scientists Say

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The spine-chilling grip of fear can become all-consuming. It triggers a cascade of self-reinforcing chemical changes within our bodies to rapidly prepare us for a threat response.

When this process goes awry, impacts can include anxiety and post-traumatic stress disorder (PTSD) – a condition that can lead to uncontrollable replays of a traumatic event, keeping people stuck in fear.

But seeing most of us are not constantly stuck in fight-flight-freeze and fawn mode, our bodies clearly have some mechanism to rein in this fear response. Researchers have just pinpointed one of these brakes within the brains of mice.

Biomedical researcher Wen-Hsien Hou, based at Yang Ming Chiao Tung University (NYCU) during the study, and colleagues found this mechanism in mouse amygdalas, part of the mammalian brain involved in memory processing and emotional responses.

When mice were conditioned to associate a specific sound with an electric shock, then threatened with that sound, a group of cells in their amygdalas lit up with activity.

“When these specific nerve cells were inhibited, the mice froze for a longer time when they anticipated an electric shock,” explains Hou.

This suggests they were experiencing more fear than peers whose ‘fear brake’ neurons had not been genetically stifled.

“These cells act like brakes, preventing excessive reactions to fear,” says NYCU neurophysiologist Cheng-Chang Lien.

Most cell circuits that hold our memories (engrams) that researchers have so far identified respond to glutamate. But this ‘brake’ circuit seems to be gamma-aminobutyric acid (GABA)-based.

Previous research has also shown a switch between these two neurotransmitters is involved in fear.

The cells involved are located in the central-lateral part of the amygdala, which acts as a sort of library for fear memories.

The newly identified neural circuit seems to control how much fear mammals express when those memories are accessed, by countering our glutamate-using fear acceleration circuits.

While humans share many physiological brain features with mice, there are differences too, so there’s still a ways to go before we can confirm this process acts the same within our own brains. But the study provides a path for finding these fear brakes within us.

Our findings shed light on the complex mechanisms involved in the formation and regulation of fear memories,” Hou and team write. “We demonstrate that selective inhibition enhances fear memory expression.”

If researchers do find an equivalent circuit in humans, scientists could then determine if it plays a role in PTSD.

This research was published in Cell Reports.

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