Fear factor

Fear factor

Could we someday selectively erase our worst fears?
October 28, 2009

Let’s say you’re wandering through a deserted alley late one foggy October night. You turn a corner, and lo and behold, you’re surrounded by a crowd of brain-thirsty zombies. Your pulse quickens, your amygdala fires, your respiration is off the charts. You try to run, but you trip and fall. As your attackers close in, ready to feast on your brains like cheese dip at a Halloween party, you wake up screaming.

Could your nightmare have been the result of bad pizza, ill-founded superstitions or the fact that you watched Michael Jackson’s Thriller video 13 times in a row on YouTube? Whatever the reason, your zombie mauling is a memory you’d rather forget. But how? New research might provide help in the future.

Last spring, researcher Sheena Josselyn of The Hospital for Sick Children and the University of Toronto succeeded in wiping out fearful memories in mice. Chronicled in the journal Science, the work of Josselyn and her team could eventually change how we deal with post-traumatic stress.

“In terms of what’s going on, fear is similar in mouse and human brains,” says Josselyn. “Observing fear in a mouse is a little harder than reading expressions of fear in a person’s face. However, mice display fear through a phenomenon called ‘freezing,’ which they do when they encounter predators or face other fearful situations.”

Josselyn’s team wanted to see whether they could delete a specific fearful memory in mice without wiping out all fear responses. To do so, they targeted the cells that were overexpressing a protein called CREB, which they introduced into mice. The fearful memory they produced gravitated like a magnet to cells that had high levels of CREB.

“Rather than going in with a sledgehammer approach and creating a mouse that wasn’t afraid of anything,” says Josselyn, “we genetically engineered mice with special biochemical markers on neurons known to be associated with fear memories.”

Her team then put the mice through a simple fear-conditioning regimen, giving them a mild shock when they heard a specific tone — just enough for them to take notice. “You only have to put your hand on a stove once to be afraid,” says Josselyn.

Once the mice associated the electrical shock with the tone, they froze with fear when they heard the tone, even when it was sounded without a shock.

After that initial conditioning, the team managed to eliminate the fear from the amygdala, the brain structure responsible for decoding emotions — particularly “fight or flight” responses. They used a toxin that selectively destroyed the neurons associated with the memory.

“We think that those memories in the mice are gone forever,” says Josselyn, “but because we look at the mice for only a few weeks after the tests, we’re not really sure.”

But even if the mouse memories are gone for good, re-creating the experiment in people is still a long way off, due to the complexity of the human brain. And Josselyn says transferring their success to humans also raises a bevy of ethical issues.

“If we can get rid of fear, what other kinds of memories could we get rid of?” she says. “And do those memories work the same way as fearful ones?” 

Far from always being negative, she adds, fear can sometimes be helpful, as when avoiding danger, or even exciting in small amounts (ask any skydiver).

“There’s something exhilarating about that sort of Halloween fear,” she says. “It’s really fun to have your amygdala fire and experience a harmless, brief scary moment or two.”