Discovery of Where Fear Begins in the Brain Could Improve Treatments for Anxiety and Phobias

fear cell
A subset of neurons shown here, called PKC delta-expressing cells, located in the brain's central amygdala, drive aversive learning in mice, neuroscientists have demonstrated. Li Lab CSHL

Fear is something that lurks in the back of our minds, and new research from Cold Spring Harbor Laboratory in New York has located more precisely where in our minds this fear originates. The finding could help us develop ways to better control and possibly even overcome our fears and anxieties.

Scientists know that the lateral amygdala, an almond-shaped structure deep in the brain, is the hub of fear. Research has suggested that the lateral amygdala turned dangerous or uncomfortable situations, such as getting bitten by a dog, into fearful associations, such as a fear of dogs. However, the biological mechanism propelling this has been unclear; until now.

A new study published online in Nature Neuroscience shows that another area of the brain, known as the central amygdala, also plays a role in creating fear; in fact, it is where fear first forms in the brain. The expression of a protein called PKC-8 then conveys unpleasant and uncomfortable experiences from the central amygdala to the lateral amygdala, where the memories are consolidated and a fear is born.

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For their study, lead researcher Bo Li and his team used mouse models in a series of experiments to better understand how fear is learned and remembered in the brain. In the first experiment, the team gave mice an uncomfortable shock to the foot. The team took brain scans of the mice as this occurred and noted that the central amygdala was stimulated before the lateral amygdala.

Knowing this, they then sought to understand what biological mechanism linked communication between these two areas of the brain. Li and his team blocked activity of the neurons in the central amygdala that control expression of a protein called PKC-delta, and repeated the foot shock experiments.

Results showed that mice with these neurons blocked displayed less activity in the lateral amygdala when exposed to uncomfortable foot shocks. According to the researchers, this result confirms that the formation of fearful associations did not begin in the lateral amygdala, as past research had taught, but must start somewhere else.

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"If the conventional view was correct, you should see normal levels of activity in the lateral amygdala - where the activity supposedly begins. But this wasn't the case," Li said in a statement.

Lastly, the researchers succeeded in creating a false memory of pain in the mice by shining light on neurons in the central amygdala to stimulate them, a process known as optogenetic stimulus. This result also confirmed that the central amygdala plays an initial and critical role in fear formation, something that was not previously known.

While fear is essential to keeping us safe and away from potentially dangerous and deadly situations, sometimes fears can develop into phobias and interfere with our ability to lead our lives.

The researchers predict their findings could be key to helping us learn to control and minimize these phobias, and could even play a role in addressing conditions such as post-traumatic stress disorder and anxiety, proving that fear really is just a state of mind.