Brain circuit that controls anxiety levels discovered

Research could help find better drugs to treat anxiety.
August 23, 2013

The tips of long neuronal extensions from the amygdala (green) contact neurons of the hippocampus (blue). This communication pathway helps to modulate anxiety. (Credit: Ada Felix-Ortiz/MIT)

Researchers at MIT’s Picower Institute for Learning and Memory  have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels.

By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels. The research could help find better drugs to treat anxiety.

Measuring anxiety

Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact.

To study those interactions, the researchers turned to optogenetics, which uses a virus that allows them to genetically engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus.

The researchers tested the mice anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges.

When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges.

In future studies, the MIT team plans to investigate the effects of the amygdala on other targets in the hippocampus and the prefrontal cortex, which has also been implicated in anxiety.

“The practical use of this innovation is the identification of a novel target for potential anxiety treatment,” Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory, explained to KurzweilAI. “While the time frame to translation to a treatment that could be used in humans is difficult to predict, we are taking the first step in developing more effective treatments for anxiety: identifying the critical neural substrates involved in controlling anxiety states.”

Anxiety disorders, which include post-traumatic stress disorder, social phobias and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects.

The research was funded by the JPB Foundation, the Picower Institute Innovation Fund, the Whitehall Foundation and the Klingenstein Foundation.


Tye Laboratory
Picower Institute for Learning and Memory
Department of Brain and Cognitive Sciences
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