In humans, anxiety is often triggered unnecessarily.
In the wild, an animal that never feels anxiety would quickly become a dead animal.
This is due to the fact that anxiety produces a raised sense of awareness and physiological readiness to fight or fly, which is essential for survival.
For many people, however, anxiety is triggered in situations where it is unnecessary or even unhelpful, such as a crowded mall or when talking to a group of friends.
For these people, anxiety becomes a problem. Rather than a sensible reaction to a life-threatening situation, anxiety becomes triggered inappropriately.
Anxiety disorders are "the most common mental illness" in the United States, affecting an estimated 40 million adults.
Because of this high prevalence, researchers are forging ahead in an effort to uncover what goes on in the brain. It is important to understand which brain circuits are controlling the anxiety response, and what goes wrong with those circuits in people with anxiety disorders.
Digging for 'anxiety cells'
The most recent study was carried out by Mazen Kheirbek, Ph.D., who works at the University of California, San Francisco, and a team from Columbia University Irving Medical Center (CUIMC) in New York.
Kheirbek explains their aims, saying, "We wanted to understand where the emotional information that goes into the feeling of anxiety is encoded within the brain." Their findings are published this week in the journal Neuron.
The team was particularly interested in the hippocampus. This region of the brain plays a role in autobiographical memory and navigation but also appears to play a role in mood and anxiety. In particular, earlier studies have demonstrated that altering activity in the ventral region of the hippocampus reduces anxiety.
To investigate this region in more detail, the scientists measured the output of hundreds of cells in mice's hippocampi while they went about their daily business. It was found that when the animals encountered a situation that made them feel anxious, the neurons in the ventral region of the hippocampus became active.
"We call these anxiety cells because they only fire when the animals are in places that are innately frightening to them. For a mouse, that's an open area where they're more exposed to predators, or an elevated platform."
Rene Hen, Ph.D., a professor of psychiatry at CUIMC
Tracing the 'anxiety cells'
The scientists then traced these cells as they traveled from the hippocampus to the hypothalamus. The hypothalamus controls anxiety behaviors — in humans, this includes the secretion of stress hormones, avoidance behavior, and increased heart rate.
Next, they artificially turned these anxiety cells off. They used a technique called optogenetics, which allows scientists to control individual neurons using pulses of light.
The scientists found that when these cells were switched off, the mice stopped producing fear-related behaviors. Conversely, when these cells were switched on, mice behaved anxiously, despite being in a safe area.
Although other parts of the brain are known to be involved in anxiety, this is the very first time that a group of cells has been found that represent anxiety regardless of the environmental stimulus that brings about the emotion.
Kheirbek explains, "This is exciting because it represents a direct, rapid pathway in the brain that lets animals respond to anxiety-provoking places without needing to go through higher-order brain regions."
Now that these cells have been described, they could provide a new direction for treating anxiety disorders.
Dr. Jeffrey Lieberman, who is the Lawrence C. Kolb Professor and chair of psychiatry at CUIMC, explains, "This study shows how translational research using basic science techniques in animal models can elucidate the underlying basis of human emotions and reasons for mental disorders, thereby pointing the way for treatment development."
Although more work will need to be done, finding a novel target for potential treatments is an exciting step forward.