A Gene for the Fear Factor

• Dr. Gleb Shumyatsky's Web Site

Rutgers geneticist Gleb Shumyatsky has discovered a gene that controls both innate and learned forms of fear. The gene, known as Stathmin or Oncoprotein 18, is highly concentrated in the amygdala, a key region of the brain that deals with fear and anxiety.

“This is a major advance in the field of learning and memory that will allow for a better understanding of post traumatic stress disorder, phobias, borderline personality disorder and other human anxiety diseases,” said Shumyatsky, an assistant professor of genetics at Rutgers,. “It will provide important information on how learned and innate fear is experienced and processed, and may point the way to apply new therapies.”

In collaboration with Nobel laureate Eric Kandel at Columbia University and Vadim Bolshakov at Harvard Medical School, Shumyatsky had previously identified another gene that controlled learned but not innate fear. The new research being reported by Shumyatski, Kandel et al. is the first major attempt to analyze how both learned and innate fear is controlled at the molecular level.

Shumyatsky, his collaborators and their laboratory colleagues used mice that were deficient in Stathmin and analyzed their anxiety levels by recording their performance in mazes. Mice instinctively avoid open spaces, but the knockout mice showed no fear and consistently explored more open areas than normal mice. Reductions in innate fear behaviors, such as avoiding open spaces as opposed to “safer” areas with less exposure, correlated with the absence of Stathmin.

The researchers relied on a combination of mouse genetics, cellular electrophysiology and behavior to support their collaborative findings, presented in the Nov. 18 issue of the journal Cell Online.

Shumyatsky explained that the earlier research paper described a gene that is expressed in the learned fear circuitry and controls only learned fear but not innate fear. The new paper describes a gene that controls both learned and innate fear. This work therefore emphasizes the importance of local gene expression in the neural circuits responsible for specific behaviors.

“This study provides genetic evidence that amygdala-enriched Stathmin is required for the expression of innate fear and the formation of memory for learned fear,” the authors concluded. “Stathmin knockout mice can be used as a model of anxiety states of mental disorders with innate and learned fear components (and) these animal models could be used to develop new anti-anxiety agents,” they added.