BioEd Online

Knock one key protein out of mice and they start behaving like fearless daredevils. Researchers say that studying these genetically engineered animals could one day yield better drugs for anxiety and post-traumatic stress disorders.

Scientists have long known that the fearful responses of both mice and men stem from a part of the brain called the amygdala. Researchers have managed to create fearless mice before by interfering with the development of the amygdala, but the damage to the brain was often so severe it was hard to know exactly what controlled the fear response.

Now Gleb Shumyatsky of Rutgers University in Piscataway, New Jersey, and his colleagues have created fearless mice by knocking out a single gene, called stathmin, which produces a protein involved in nerve-cell communication.

Shocking indifference

The mice displayed a relative indifference to electrical shocks and, unlike normal mice, were quick to ignore a tone that they had previously learned to associate with those shocks. Normal mice would freeze in fear upon hearing the sound, but the daredevil mice were happier to go about their normal business.

The altered mice also boldly explored open spaces in the environment, something that normal mice would avoid.

So were the altered mice just being stupid, rather than brave? The researchers say no. The mutant and normal animals performed equally well on a memory test in which they had to recall the location of a dry platform in a water maze. The results of the study appear this week in Cell¹.

Total recall

The stathmin protein controls the development of much needed structural support molecules inside nerve cells, and is expressed mostly inside the amygdala (and also in the testes).

Without support structures, neurons apparently fail to develop normal connections with each other. And that affects memory formation in this emotional centre of the brain.

Shumyatsky hopes to continue investigating the role of stathmin. "Understanding the molecules that regulate fear would allow us to characterize the basic mechanisms of memory formation," he says.

Further research could also help drugmakers to design better medicines, Shumyatsky adds. "It would shed light on how pharmacological agents can be designed to treat anxiety disorders."