In the laboratory, fear can be conditioned by linking a neutral stimulus, such as a light or sound, to something unpleasant or painful, such as an electric shock, he explained. That process of learned association occurs in a portion of the amygdala called the lateral nucleus.
As a first step to unravel the molecular events underlying fear learning, Shumyatsky's group recently identified several genes present at particularly high levels in the lateral nucleus and in the structures that relay information about learned and instinctive fear to the amygdala. One such gene was stathmin.
In the current study, the researchers found that the brains of mice lacking stathmin showed an unusual number of microtubules, which are structural components of the cytoskeleton. Stathmin normally controls the assembly and breakdown of the cellular scaffolds, Shumyatsky explained.
"For memory, the brain needs to quickly disassemble and rebuild microtubules to form connections where they are needed," Shumyatsky said. "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."
Indeed, the researchers found impairments in the ability of key inputs in the animals' brains to form connections between neurons. Such connections form the cellular basis for learning and memory.
To relate these brain abnormalities to behavior, the team then exposed normal and stathmin-deficient mice to a neutral tone while delivering a mild electric shock. While both groups displayed some fear response by freezing immediately after a shock and later after hearing the tone, knockout mice reacted less strongly, they found, suggesting that they had an impaired ability to learn fear.
In other tests, the mutant mice also showed less instinctive fear of open spaces, venturing out into environments they would usually av