Rebecca Shansky

Researchers’ preclinical trial upends conventional wisdom about responses to fear

by Thea Singer

Fear. You’ve been there: Your heart races, even jumps to your throat. Your hands grow clammy and your stomach churns. Your mind goes blank.

Rats have been there, too. We don’t know their feel­ings, of course, but we do know their response: They freeze in their tracks. Or at least that’s been the con­sensus among sci­en­tists since 1899, when exper­i­mental psy­chol­o­gist Willard Stanton Small first noted the behavior.

But now new research led by Rebecca Shansky, assis­tant pro­fessor of psy­chology at North­eastern Uni­ver­sity, upends that con­ven­tional wisdom.

In a study recently pub­lished in the online journal eLife, Shansky’s team found that female rats often respond to fear by “darting.” “They start run­ning around like crazy,” Shansky says. “It looks like they’re trying to escape.”

In addi­tion, the darting rats were more suc­cessful at inte­grating a process that sup­pressed the fear response, says Shansky, exhibiting a “cog­ni­tive flex­i­bility” that the freezers lacked.

The find­ings not only raise ques­tions about the veracity of pre­vious studies that rely on freezing to indi­cate fear. They could also lead to better treat­ments for post-​​traumatic stress dis­order, a con­di­tion that, in the U.S. alone, affects about 8 mil­lion adults during a given year, according to the National Center for PTSD of the U.S. Depart­ment of Vet­erans Affairs.

If we can har­ness what­ever is going on when an animal becomes a darter,” says Shansky, “we could try to apply that to treatments.”

An unex­pected finding

Shansky had not set out to chal­lenge a century-​​old assump­tion. Rather, she stum­bled across the find­ings while per­forming a common behav­ioral test called “fear con­di­tioning” in an effort to see how indi­vidual males and females dif­fered in their fear responses, and to explore what brain changes related to those differences.

The test involved teaching the ani­mals to asso­ciate a tone with a foot shock, and then—with a video camera con­nected to a computer—measuring the dura­tion of their reac­tion as the training pro­ceeded. “Ani­mals who exhibit low levels of freezing would tra­di­tion­ally be inter­preted as either not learning or nat­u­rally fear­less,” says Shansky.

Because com­puters may mis­take sleeping for freezing, grad­uate stu­dent Tina Gruene, PhD’19, watched the videos after­ward as a backup check. What she saw shocked her: Scores of the female rats not only didn’t freeze at the sound of the tone; they darted hither and yon, as if looking for an exit.

What did that mean? The study had a large number of rats—120 as opposed to the stan­dard 20—so Shansky set out to quan­tify the behavior. “We wanted to see if this was some­thing real,” she says.

The researchers fed the videos into a behav­ioral analysis pro­gram that tracks motion to mon­itor the velocity of the ani­mals’ move­ment. Their plotted graphs con­firmed their hunch: Darting was not a sign of fear­less­ness or an inability to learn. It was just as much a learned response as freezing.

The learning curve for darting was the same as the learning curve for freezing,” says Shansky, pointing to graphics in the paper. “But we saw it almost exclu­sively in the females—more than 40 per­cent of them.”

Better treat­ments

The find­ings go beyond clar­i­fying dif­fer­ences in fear behavior among male and female rats. They also point to pos­si­bil­i­ties for better treat­ments for people with PTSD.

Fol­lowing the fear con­di­tioning, the researchers used a process called “extinc­tion” to sup­press the rats’ fear response: By playing the tone repeat­edly without the shock, a “good” memory may come to replace the bad one. Extinc­tion is akin to expo­sure therapy for people with PTSD. Expo­sure therapy works, but not for everyone: it’s effec­tive in only about 50 per­cent of cases, according to numerous studies, and it has a very high dropout rate.

The darters, it turned out, were more suc­cessful at extinc­tion than the freezers, sug­gesting that the neu­ro­bi­o­log­ical processes of the males and females dif­fered; the females, it appeared, had an edge. “Females may have devel­oped adap­tive strate­gies to fearful events,” says Shansky.

The results raise the ques­tion of whether PTSD treat­ments for women—who develop the dis­order twice as fre­quently as men—should be dif­ferent from those for men. Even more rad­i­cally: Might it be pos­sible to develop a therapy that alters the neural cir­cuits of freezers to more closely resemble those of darters?

Shansky expresses the spec­u­la­tion more suc­cinctly: “What if we could turn freezers into darters?” she asks.

Originally published in news@Northeastern on January 28, 2016

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