Surprising Discovery of an Anxiety-Reducing Circuit Within the Brain’s ‘Fear’ Center

Karl Deisseroth, M.D., Ph.D. - Brain & behavior research expert on anxiety
Karl Deisseroth, M.D., Ph.D.

From The Quarterly, Spring 2011

Brain & Behavior Research Foundation Scientific Council Member Karl Deisseroth, M.D., Ph.D., of Stanford University, has conducted a series of experiments to more precisely tease out neural circuits inside the amygdala under the thesis that knowing more about them could lead to better therapeutic solutions for excessive fear and anxiety. Most existing anti-anxiety drugs are only partly effective, and some have significant side effects. Dr. Deisseroth used a cutting-edge method he invented with the help of his 2005 NARSAD Young Investigator Grant called optogenetics in his study.

In developing optogenetics, Dr. Deisseroth discovered a way of using beams of colored light to activate specific types of nerve cells in the brains of living mice. This remarkable technology is based on a genetic “trick”: breeding strains of mice whose nerve cells are photosensitive. When light of a particular wavelength is carried along a thin fiber optic wire into such an animal’s brain – something that can be done painlessly and does not restrict the animal from moving about freely – scientists can switch individual neurons and specific neural pathways ‘on’ and ‘off’ at will.

In a newly published paper, Dr. Deisseroth’s team describes using optogenetics to target a specific circuit in the mouse’s amygdala – which is quite similar to its human counterpart. For many years scientists have understood that the amygdala is important in the processing of certain kinds of emotional responses, among them fear. It
is also commonly assumed that something in the amygdala is amiss in people who suffer from anxiety disorders. But what, exactly, and how can this be most effectively addressed?

While the amygdala has usually been associated with the ‘fear’ response, Dr. Deisseroth’s team showed that stimulation of a specifically targeted circuit actually made the mice rather bold – in other words, the very opposite of anxious. “The effect was instantaneous and could be seen as soon as the light was switched on,” Dr. Deisseroth says. Conversely, when the team used a different wavelength of light to inhibit the same amygdala circuit, the mice instantly began to manifest anxious behaviors.

It has been estimated by the National Institute of Mental Health that more than 1 in 4 Americans (28%) will suffer a clinically important anxiety-related condition over the course of their life- time. Therefore, finding a specific amygdala circuit that can be stimulated to reduce anxiety is important: it could affect the development of improved treatments.

Dr. Deisseroth says the study underlines the importance of tracing and understanding the functional dynamics of specific pathways within brain structures, in the continuing effort to find out the specific causation of psychiatric illness.