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Can fearful memories be erased?

In the movie Eternal Sunshine of the Spotless Mind, Joel and Clementine's relationship ends so sourly that the couple elects to have their mutual memories swept away via a non-surgical procedure called "targeted memory erasure." No such tool actually exists. Even the most intense therapies can't completely erase troubling or fearful memories in adults. Yet, if two young rats fall in and out of love—or, more likely, have a close encounter with a subway car—permanent memory erasure may actually be possible, previous research has suggested. So, what happens in a growing rodent brain to cause this change?

A new study on mice uncovers some answers that could someday offer a potent target for eliminating the recurrence of bad memories in humans, especially known to those who suffer from post-traumatic stress disorder (PTSD).

"Fear memories are the most robust memories—they can last over a lifetime," says Nadine Gogolla, a biologist at Harvard University and lead author on the paper published today in the journal Science. "You can push them far back, but spontaneous recovery and relapses will happen." Until now, science has been unable to stop this process—in humans or in mice. 

By repeating the previously reported rat findings, Gogolla and her colleagues found that at some point during a young mouse's development—between about 16 and 23 days postnatal—a molecular net of sorts is cast over a region of the brain called the amygdala, effectively crystallizing formerly malleable memories.

"It looks just like what you would expect from a fisherman's net," says Gogolla of the protein matrix under the microscope. "And it acts as a structural constraint on the cells. How it does that, nobody really knows." But the result is that memories are held inside. 

What the researchers did learn was that by cutting that net—with an injection of an enzyme that digests the chains linking the matrix together—memories could be once again destabilized.

"The drug cuts the net into its pieces," Gogolla says, "just like when you cut the strings of a net and it falls apart." Then, for a couple weeks, the original youthful plasticity in the neuronal circuits of the amygdala is regained and any bad memory formed after the matrix digestion could be subsequently eliminated through "extinction" therapy, a common treatment during which a patient is presented with the original fear trigger but in a context that is not fearful. When the treatment was given after a mouse underwent fear conditioning, however, extinction was unable cut out that memory completely.

"Because the treatment has to occur before a traumatic event, it's hard to make it immediately available," notes Gogolla. "But it does help us in finding the underlying mechanisms." Eventually, she hopes tools can be found that can be applied after fear-inducing experiences, and that translate from mice to humans. This would be welcome relief for the approximately 20 percent of all military personel who have returned from Iraq and Afghanistan reporting symptoms of PTSD, not to mention for heartbroken couples.

Also see our podcast on this research.

Picture by Don89 via iStockphoto

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