Leaving The Comfort Zone: One Brain Molecule Controls Anti-Social Behavior

By Einat Paz-Frankel, NoCamels August 30, 2016 3 minutes

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Meeting new people can be stressful or rewarding, depending on your personality. A new Israeli study suggests that one molecule involved in regulating stress in the brain may help determine how willing we are to leave the comfort zone of our social group and strike up new relationships.

In the Weizmann Institute study, published recently in Nature Neuroscience, the researchers identified a stress mechanism in mice that appears to act as a ‘social switch.’ It caused mice either to increase interactions with ‘friends’ and ‘acquaintances’ or, in contrast, to reduce such interactions and seek instead to meet strangers. Since an analogous stress system operates in the human brain, the findings suggest that a similar mechanism may regulate coping with social challenges in humans. Disruptions in this mechanism might be responsible for difficulties with social coping in people affected by social anxiety, as well as in autism, schizophrenia and other disorders.

Stress-coping molecule Urocortin-3 (green) and its receptor, CRFR2 (red), expressed in the mouse brain region responsible for social behavior [viewed under a microscope]. Courtesy of Weizmann Institute

Conducted by Prof. Alon Chen, Dr. Yair Shemesh and Oren Forkosh, the study suggests that “most social contacts involve a certain level of social stress or anxiety, even when we interact with people we know well, for example, during a holiday meal with extended family,” Shemesh said in a statement. “In fact, from the point of view of evolution, moderate levels of social apprehension are essential for safe and successful social engagement.”

According to Chen, “in social environments, an individual’s interests often clash with the group’s needs and expectations. So, the individual must maintain what’s known as a socio-emotional balance, between the processing of social signals and his or her emotional response to such pressure.”

The scientists used two behavioral setups to study how mice cope with the challenge of interacting with other mice. One was a ‘social maze,’ in which a mouse can choose whether to interact through a mesh with familiar mice or with strangers, or even to avoid interaction at all. The other was a special arena, in which a group of mice was tracked with video cameras and the observations were analyzed with a computer algorithm created for this purpose. This setting enabled the researchers to quantify various types of interactions – such as approach, contact, attack or chase – among individual mice within the group over several days.

A molecule responsible for decisions such as switching jobs or apartments

The results revealed that a molecular mechanism involved in stress management in the brain of mice determines their behavior toward other mice. The mechanism involves a small signaling molecule, Urocortin-3, and a receptor on the surface of neurons to which this molecule binds. Both Urocortin-3 and the receptor are part of the corticotropin-releasing factor, or CRF system, a hormone that plays a central role in coping with stress. Both are prominently expressed in a brain region called the medial amygdala, known to be associated with social behavior in mice.

Mice that had high levels of Urocortin-3 in the brain actively sought out contacts with new mice behind the net, even ignoring their own group. But when the activity of Urocortin-3 and its receptor was blocked in their brains, the mice chose to socialize mainly within the group, avoiding contacts with strangers.

According to Forkosh, “in nature, mice live in groups, and the social challenges they face within the group differ from their relationship with intruders. It therefore makes sense for a brain mechanism to produce different types of social coping in these two situations. In humans, this mechanism might be involved whenever we consider moving out of our parents’ home, getting a divorce or changing jobs or apartments.”