Anxiety cells discovered in…anxious mice?

By Liz Meszaros, MDLinx
Published February 14, 2018

Key Takeaways

Neuroscientists at Columbia University Irving Medical Center (CUIMC), New York, NY, and the University of California, San Francisco (UCSF) have discovered “anxiety cells” inside the hippocampus in the brains of mice, and think that such cells may also exist in humans. They published their results recently in Neuron.

Previous studies have identified many other brain cells that play a role in anxiety, but these cells are the first to be found that may represent the state of anxiety.

“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,” said co-senior investigator Mazen Kheirbek, PhD, assistant professor of psychiatry, UCSF. 

These anxiety cells send out messages to other neural areas to turn on anxious behaviors. In mice, this includes avoidance of dangerous areas or fleeing to a safe area.

“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,” said Rene Hen, PhD, professor of psychiatry, CIUMC, one of the senior investigators.

Anxiety is a normal and necessary response to a threat. An animal’s safety depends on avoiding environments that may expose them to predators, and anxiety evokes the necessary avoidance behaviors.

In people with anxiety disorders, this ‘healthy’ anxiety goes into overdrive and is no longer healthy. To discover what goes wrong in humans, Dr. Hen and colleagues have been studying mice to determine how the brain processes healthy anxiety.

Focusing on the hippocampus

The hippocampus—linked to new memories and the ability to navigate through complex environments—has recently been shown to have a role in mood regulation. Researchers have shown that changing brain activity in the ventral part of the hippocampus can reduce anxiety. The hippocampus also sends signals to other areas, including the amygdala and hypothalamus, which also control anxiety-related behavior.

In this study, Dr. Hen and colleagues recorded the activity of hundreds of hippocampal cells as the mice moved through their surroundings. When the mice were in exposed, anxiety-provoking environments, specific cells in the ventral part of the hippocampus were activated. The more anxious the mice, the greater the cell activity.

Scientists used a technique known as ‘optogenetics’ to control neuronal activity using beams of light, allowing them to turn these cells ‘off’ and ‘on.’ In doing so, they found that the anxiety cells controlled anxiety behavior. When the cells were ‘off,’ the mice stopped exhibiting fear-related behavior. When the cells were ‘on,’ the mice exhibited more fear behavior, even when they were in a safe environment.

The discovery of these specific anxiety cells brings the possibility of specific targeted treatments to reduce anxiety.

“Now that we’ve found these cells in the hippocampus, it opens up new areas for exploring treatment ideas that we didn’t know existed before,” said lead author Jessica Jimenez, PhD, an MD/PhD student at Columbia University’s Vagelos College of Physicians & Surgeons.

“We’re looking to see if these cells are different molecularly from other neurons,” said Dr. Hen. “If there’s a specific receptor on the cells that distinguishes them from their neighbors, it may be possible to produce a new drug to reduce anxiety.”

The study was supported by grants from the National Institutes of Health, Intelligence Advanced Research Projects Activity, Defense Advanced Research Projects Agency, NY STEM awards, and the Weill Scholar Award program.

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