Discovery of brain's first known 'safety circuit' gives new perspective on anxiety disorders

Apr 20 2005

Scientists at Columbia University Medical Center have made a surprising finding about positive emotions that should change the way people think about anxiety disorders.

The researchers – Michael Rogan and Nobel laureate Eric Kandel – discovered that a previously unknown "safety circuit" exists deep within the brain and is responsible for the good feelings associated with safety and security. The findings appear in the April 21 issue of Neuron.

"This work points to a second system – in addition to the brain's well-known fear circuits – that probably malfunctions in some people with anxiety disorders," says the study's first author, Michael Rogan, Ph.D., of Columbia's Center for Neurobiology and Behavior. "This opens up hope for other types of treatment that can act on your sense of safety and security."

The new safety circuit may also lead to a better understanding of addiction since the circuit operates in the same part of the brain known to be involved in addiction. "There's a feeling of invulnerability that comes with alcohol and other drugs," Dr. Rogan says. "Addicts frequently say, 'I had my first drink, and I felt safe for the first time,' so it may be that drugs of abuse artificially activate some aspect of this safety mechanism."

Most anxiety research focuses on the brain's fear circuits and it's easy to understand why. Fear, after all, is the problem in anxiety disorders. "When someone goes to a psychiatrist in terror or grinding anxiety, the doctor doesn't think about the patient's happiness issues," Dr. Rogan says.

Yet the neurobiology of happiness, which has generally been ignored by researchers as well as physicians, may be equally important in the disorders. "The missing part of our picture of anxiety is the good feelings associated with being safe and secure," Dr. Rogan says. "But positive emotions are harder to study in the lab than negative emotions like fear. How do you know when you've made a mouse feel safe and secure?"

The experiments described in the Neuron paper do exactly that. Michael Rogan trained mice to recognize that they were safe from danger (mild electrical shocks) when they heard a particular sound. He then recorded what happened in the mice brains before and after they heard the safety sound.

As expected, in accordance with previous theories, information about the safety sound traveled through the brain's fear circuits and reduced the amount of activity in the brain's fear center, the amygdala.

"Researchers have generally talked about safety in terms of a reduction of fear, and it's no surprise that we found that the safety sound reduces neural activity in the amygdala," Michael Rogan says.

But Rogan and Kandel also found that the safety signal traveled through other, previously unknown circuits that lead to the brain's caudoputamen, a region known to be involved in motivation and reward. This region became more active when the mice felt safe and secure.

"Our results show there's more to the feeling of safety and security than the simple absence of danger," Michael Rogan says. "We have found that there is another part of the brain that is involved in calculating how much protection or shelter is in the environment. Shelter is something that is independent of the presence or absence of danger, and it contributes to a sense of well being."

The next step, Rogan says, is to verify that the same safety circuits are present in people. He is now planning a brain imaging study that will look for activity in the caudoputamen of people conditioned to link a sound with safe conditions in the midst of aversive events (in this case, a blood-curdling human scream, not electrical shock).

Eric Kandel, the senior author of the paper, is University Professor and Kavli Professor at the Center for Neurobiology and Behavior at Columbia University, and a Senior Investigator at the Howard Hughes Medical Institute.