In his 1933 inaugural address, US President Franklin Roosevelt told a seriously Depressed nation (with a capital D) that “the only thing we have to fear is fear itself.” Sure, it was political rhetoric, but FDR was, perhaps, on to something that scientists wouldn’t discover for another 70 years: Fear is not just an emotion. It’s a physical substance.
Fear is a protein. It’s called stathmin.
When scientists deleted the gene that encodes stathmin in mice, it resulted in the uninhibited mischief of a new breed of mighty mouse. They couldn’t fly, but, according to a study published in the November 18, 2005 issue of Cell, the mice began taking uncharacteristic risks.
If you’ve ever seen a mouse indoors—most likely from a chair-top perspective—you may have noticed that it was running along the edge of the room. Mice are comfortable running along the edges of things and they do the same in lab mazes.
After blocking stathmin production in a group of mice, researchers compared the amount of time mice spent in the perceived safety of a maze’s perimeter to the time spent on the open road of its interior. Mice lacking the stathmin gene spent 50% more time off the walls than did mice with the gene.
“They aren’t completely fearless,” said Gleb Shumytsky, assistant professor of genetics at Rutgers University and lead author of the study, “but they have less fear.”
Further experiments also found the mice displaying courage. Interestingly, no change in memory or reasoning appeared after the gene deletion.
Stathmin is produced almost exclusively in the lateral nucleus of the amygdala, the small, almond-sized part of the brain responsible for mediating emotions. (Cells in the testes also express stathmin; “having the balls” may aid an individual in undertaking a risk venture.)
“This is really a tiny, tiny, tiny structure,” said Vadim Bolshakov, an assistant professor from Harvard Medical School and a coauthor of the paper, about the amygdala’s subnucleus. “It’s amazing that it could be implicated in such an important biological function.”
In addition to Rutgers and Harvard Medical School, researchers from Columbia University (including Nobel laureate Eric Kandel) participated in the study. Previously, the group demonstrated that stathmin can quell learned fears. Their new finding shows that stathmin is able to mediate innate fears.
A biochemical analysis connected stathmin deficiency with microtubules, molecular railroads that go from the nucleus to the synapse within the amygdala’s cells. Microtubles become more stable and less flexible in the absence of stathmin. According to Shumytsky, a drug that deactivates stathmin, or prevents the expression of the gene that produces it, could cause a surge in courage.
“It would go directly to the amygdala and fear-related structures,” he said. “It would be specifically targeting this behavior but not anything else in the brain.”
Bolshakov cautions that there’s a spectrum of fear, which can’t be assigned to a single gene. As in the mighty mice, a drug that inhibits stathmin isn’t going to remove fear completely.
But don’t tell that to the mice, who, after generations of oppression at the paws of cats, may be plotting their revolution.
Originally published November 29, 2005
