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“Our understanding of the more precise circuitry within the amygdala is just now beginning to take off,” says Kerry Ressler, a neuroscientist at Emory University who was not involved in the study. “Optogenetics, where scientist can activate specific cell populations and even parts of cells, is a powerful approach to dissect how the amygdala modulates fear and anxiety.”

Ki Ann Goosens, a neuroscientist at MIT who was not involved in the study, says the research could help explain individual variation in baseline anxiety levels. “The findings tell us that this circuit contributes to an individual set point for anxiety,” she says.

“It may be a theme that some major sources of dysfunction in psychiatric disorders lie in the flow of information between different brain regions,” says Deisseroth. “This is something that optogenetics is uniquely suited to address.”

Researchers hope the discovery will ultimately enable the development of new treatments for anxiety disorders that are free of the side effects of existing drugs. Benzodiazepines, such as valium, are sedating and carry the risk of addiction. Mice given benzodiazepenes become less fearful and more exploratory, but the drug also affects their movement, making them sluggish, says Tye. Activating the circuit with light doesn’t seem to elicit this problem. “These animals are sniffing, grooming, doing everything normally,” she says.

To make more selective anti-anxiety drugs, scientists would need to target only the subset of cells that make up this circuit, which may prove difficult to do chemically. But Deisseroth is already working on another approach, using a noninvasive method of stimulating the brain called transcranial magnetic stimulation (TMS).  The technology uses magnetic fields to activate neurons on the surface of the brain, and is approved by the Food and Drug Administration to treat depression. By combining TMS and functional brain imaging, Deisseroth is now examining whether it’s possible to noninvasively stimulate specific circuits in the human brain. His first study, which has just begun, will focus on a circuit that his team has previously linked to Parkinson’s disease.

Tye is working to better understand the role that the circuit identified in the current study plays in fear as opposed to anxiety. While the two terms tend to be interchangeable in everyday usage, neuroscientists define fear as a response to a specific thing—a loud sound, for instance, or oncoming traffic. Anxiety, on the other hand, is chronic, generalized fear. “Fear can be important for survival, but anxiety disorders are maladaptive,” says Tye.

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Credit: Deisseroth lab
Video by Karl Deisseroth, Stanford University

Tagged: Biomedicine, cancer, brain, optogenetics, anxiety

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