Where do fear and anxiety reside in the brain? New cells identified

The human brain operates like an enigma, filled with mysteries waiting to be uncovered. For years, we’ve known that a small, almond-shaped region within the brain, the amygdala, plays a pivotal role in controlling emotional reactions. Yet, we’ve barely scratched the surface in understanding how its cells function, especially in relation to fear and anxiety.

But now, the veil is lifting. Scientists at UC Davis have embarked on a mission to demystify the amygdala, and their findings could revolutionize the way we treat disorders such as anxiety and depression.

Amygdala cell clusters and anxiety

Just like the vast universe, the brain carries extensive mysteries within its tiny structure, and the amygdala is one of the most intriguing.

The amygdala is the emotional powerhouse of the brain and plays a leading role causing feelings of fear and anxiety.

“The amygdala is central to emotion processing in the brain, and is known to contribute to fear and anxiety,” said Drew Fox, associate professor in the UC Davis Department of Psychology and senior author on the paper.

His team’s remarkable research aims to unravel the secrets held within the depths of the amygdala.

Limitations of past research

Previously, we believed that the cells, size, or structure of the amygdala could predict emotional issues like anxiety.

This conviction has since proven unfounded. Our understanding has evolved, realizing that the overall size and structure bear little relevance to the emotional problems one might encounter in life.

Fox asserts that emotional disorders most likely surface due to alterations in specific cell types, each with their own distinct functions. The challenge, however, lies in identifying these cell types in human and non-human primates.

Power of collaboration

To bridge this knowledge gap, a dynamic collaboration was initiated. Shawn Kamboj, a graduate student, led the research endeavor with Fox’s research group and Professor Cynthia Schumann’s lab at the UC Davis School of Medicine.

The objective was clear – to identify different cell types within subregions of the amygdala, based on the genes they express.

Unraveling the amygdala mysteries

Through a method called single-cell RNA sequencing, the researchers were able to identify, cluster, and understand the origin of different cells within the amygdala, unlocking new doors to potential treatments of anxiety.

The genes involved in anxiety and other disorders were focused upon. Fox believes this strategy can help single out cell types that could possibly lead to psychopathology.

One group of cells they identified expressed a gene called FOXP2. This gene is found in cells at the edge of the amygdala, referred to as intercalated cells.

In rodents, this small group of FOXP2-expressing cells plays a crucial role as “gatekeepers,” managing signal traffic in or out of the amygdala. This finding points toward intercalated cells as a potentially powerful platform for developing new treatments.

Human vs. non-human primate

Another significant observation made by Fox and his team was the similarities and differences between cell types in human and non-human primate amygdalas.

Understanding these similarities and differences could help us understand how findings in animal models of disorders like anxiety and autism can be related to humans.

Cell clusters to treat anxiety

This research also hints at potential new treatment strategies. FOXP2-expressing cells, for instance, express both anxiety-related genes and a receptor that can be targeted by drugs, called Neuropeptide FF Receptor 2 (NPFFR2).

This information could guide the development of drugs that activate the NPFFR2 pathway and help treat anxiety-related disorders.

Research on amygdala cells and anxiety

With a more refined understanding of the amygdala and the cell types involved, we may soon have the capability to identify and target “chokepoints.”

These are points that affect a vast number of people experiencing severe and incapacitating anxiety. “Put simply, if we’re developing a drug to target the amygdala, we want to know which cell type we are targeting,” Fox said.

The research by the team at the University of California, Davis, asserts that we’re on the cusp of a new era where we’ll have a more thorough understanding of the human brain and how it operates.

The journey is far from over, but every step takes us closer to a future where we can efficiently treat disorders like anxiety, bringing relief to millions worldwide.

The study is published in the American Journal of Psychiatry.

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