Humans and other animals engage in generalization--applying information acquired in one situation to similar situations. But when this cognitive strategy goes awry, people can become fearful of situations that are not dangerous.

In a study published online on May 12 in Molecular Psychiatry, Jelena Radulovic, M.D., Ph.D., and colleagues identified a neurobiological mechanism that may explain why individuals fear things or situations that are not threatening. The researchers first conditioned mice to fear situations associated with electric shocks. When the animals were then exposed to social stress, the negative experience enabled the past negative shock memories to drive aversive behavior in the absence of actual danger. Combining molecular, cellular, and circuit findings, the researchers showed that stress-induced changes of cholinergic signaling were the main mediator of the observed fear generalization. The finding suggests that correcting abnormal cholinergic signaling in specific brain circuits may be a promising therapeutic strategy for helping people with anxiety disorders, the most common psychiatric illnesses in the U.S.

Dr. Radulovic is professor in the Dominick P. Purpura Department of Neuroscience, and of psychiatry and behavioral sciences, and is the Sylvia and Robert S. Olnick Chair in Neuroscience at Einstein. She is also co-director of the Psychiatry Research Institute at Montefiore Einstein.