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Scientists have found a novel circuit in the mouse brain that controls fear and represents an ideal target for new therapies to treat anxiety disorders.

Researchers at Cold Spring Harbor Laboratory (CSHL) said that fear is stored within a distinct region of the brain.

"In our previous work, we discovered that fear learning and memory are orchestrated by neurons in the central amygdala," said CSHL Associate Professor Bo Li, who led the team of researchers.

They wanted to determine what controls the central amygdala and one possible candidate was a cluster of neurons that form the PVT, or paraventricular nucleus of the thalamus.

This region of the brain is extremely sensitive to stress, acting as a sensor for both physical and psychological tension.

The researchers looked to see if the PVT plays a role in fear learning and memory in mice.

"We found that the PVT is specifically activated as animals learn to fear or as they recall fear memories," said Li.

The team was able to see that neurons from the PVT extend deep into the central amygdala. Disrupting the connection significantly impaired fear learning.

Since the link between the PVT and the central amygdala is a critical component of fear learning, it represents an ideal target for potential drugs to treat anxiety disorders, researchers said.

To see how this link is established, researchers looked to data from people with post-traumatic stress disorder (PTSD) to identify chemical messengers that might connect the two structures.

They focused on a molecule called BDNF that has been implicated in anxiety disorders. BDNF is a well-known neural growth factor that plays an important role in stimulating the birth of new neurons as well as new connections between neurons.

Patients with anxiety disorders frequently have mutations in BDNF, suggesting that it might have a role in fear learning and memory.

The researchers worked to determine if BDNF plays a role in fear, and specifically if it affects the connection between the PVT and central amygdala in mice.

They found that the addition of BDNF in the central amygdala acutely activates its neurons, triggering a fear response in animals that have not previously been exposed to a fearful stimulus, and promoting the formation of long-term fear memories.

"We established that this is a regulatory circuit that controls fear in mice: BDNF is the chemical messenger that allows the PVT to exert control over the central amygdala," Li said.

"Our work provides mechanistic insight into a novel circuit that controls fear in the brain, and provides a target for the future treatment of anxiety disorders," said Li.

The study is published in the journal Nature.

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