March 21, 2011

Scientists Switch Off Brain’s Anxiety Circuit

Illustration of nerve cells

Using a light-based technique called optogenetics, scientists have identified a distinct brain circuit that seems to switch anxiety off and on in the mouse brain. The findings could have implications for developing improved anti-anxiety medications for humans.

Anxiety disorders affect nearly 1 in 5 American adults each year, leading to excessive feelings of fear and uncertainty that last for 6 months or more. Symptoms can intensify without treatment. Current anti-anxiety medications, however, are not always effective. Some are also addictive and have disruptive side effects, such as impaired thinking or breathing problems.

Research suggests that the amygdala — a small structure located near the base of the brain — plays a key role in anxiety. However, the neural circuits that control anxiety remain poorly understood.

To learn more about the wiring of anxiety pathways in the brains of mammals, Dr. Karl Deisseroth and his colleagues at Stanford University used a new technology called optogenetics. The technique, developed in their lab a few years ago, uses genetic engineering to add light-sensitive proteins to specific nerve cells in the mouse brain. Scientists can then activate or suppress these nerve cells by shining different wavelengths of light, via optical fibers, to specific brain regions. The new work was funded in part by NIH's National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA) and an NIH Director’s Pioneer Award.

As reported in the March 9, 2011, advance online edition of Nature, the scientists focused on long projections of nerve cells that link the basolateral subregion of the amygdala to the central nucleus of the amygdala. Research by a different Stanford team had shown abnormal functional MRI activity in these regions among patients with generalized anxiety disorder.

Mice typically shy away from open spaces, which might expose them to predators. But when Deisseroth's team used light to selectively stimulate the long nerve cell projections in the mouse amygdala, the animals’ anxious behavior changed immediately and dramatically. The mice seemed emboldened, spending more time exploring open spaces than control mice.

In contrast, when the nerve cell projections were suppressed by light in a different group of mice, the animals instantly became more anxious and risk-averse. They stayed along the walls and never ventured into the middle of the test chamber.

The researchers say their findings demonstrate the importance of studying well-defined projections between brain regions, instead of simply focusing on particular types of cells. These results implicate a precise circuit that seems important to anxiety control.

"Anxiety is a poorly understood but common psychiatric disease," says Deisseroth. "The discovery of a novel circuit whose action is to reduce anxiety, rather than increase it, points to new conceptualizations of anxiety, as well as its regulation and treatment."

— by Vicki Contie

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