Gene That Saves Mice From Being Foolhardy Identified

Fear is all in the genes: mice lacking the gene stathmin become daredevils, unable to show the appropriate fear of predators or dangerous situations, according to a report in the journal Cell.

"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 Gleb Shumyatsky, a geneticist at Rutgers University, New Jersey, who led the work. "It will provide important information on how learned and innate fear is experienced and processed, and may point the way to apply new therapies."

Professor Shumyatsky conditioned fear into one group of normal mice and another lacking the stathmin gene by making them associate an electrical shock with a particular sound. While both groups showed some fear by freezing immediately after the shock and, later, after hearing the tone, the researchers found that the stathmin-deficient mice reacted less strongly. They also showed less fear of open spaces, exploring the kinds of environments they would naturally avoid.

The work led on from Prof Shumyatsky's discovery in 2002 of gastrin-releasing peptide, a gene active in parts of the brain which deal with learned fear. In the new study, he describes how stathmin controls both learned and innate fear.

"Biologically, innate fear is something that an animal does not have to learn," said Prof Shumyatsky. "It is often species-specific - for example, mice are afraid of snakes, rats, cats. Basically animals often have inborn fear for their natural predators or certain body movements that are predator-like."

On the other hand, learned fears are a result of an animal's experience.

Because fear plays an essential role in survival, memory for fear is easily established and resistant to being deleted.

Stathmin is active in the amygdala, a part of the brain which acts as an alarm bell, and other parts of the brain that send the amygdala information. The gene helps in forming new memories. It prevents the formation of microtubules - needed when new cells are formed.

"For memory, the brain needs to quickly disassemble and rebuild microtubules to form connections where they are needed," said Prof Shumyatsky. "It appears that loss of stathmin might interfere with this ability in the amygdala, leading to the overproduction of microtubules in certain areas. In essence, the cells lose their flexibility." This loss prevents new memories being formed.