Memories of fear can be found and erased in mice, researchers show

Friday, March 13, 2009
The Canadian Press
In a scientific development that seems ripped from the script of the 2004 movie Eternal Sunshine of the Spotless Mind, Toronto researchers have shown they can find and selectively erase fear memories from the brains of mice.

The research is notable not just because the team managed to zap fear memories. Locating where the memories were stored in the first place is being hailed as a major accomplishment.

“This really then is a proof of principle that these are really the neurons that are involved in storing this kind of memory,” said Dr. Michael Salter, head of the program in neurosciences and mental health at Toronto’s Hospital for Sick Children, where the research team is based.

The study, published Thursday in the journal Science, was led by Sheena Josselyn and Paul Frankland, partners in research and in life. The couple just had a baby and were unavailable for interviews, though Josselyn — the senior author — described the work in an interview that was podcast by Science.

She and others were quick to say that it remains to be seen if the mice findings can be translated into therapies for people suffering from crippling fears provoked by traumatic memories or from post traumatic stress disorder.

“Whether it works for other types of memory … or whether it would work in another type of mammal — say a human — we don’t know,” Josselyn said in the Science podcast.

Josselyn and her team had earlier reported that neurons in the lateral amygdala that produce high levels of a protein called CREB seem to be activated when fears triggered by sounds are imprinted on the brains of mice. The amygdala is known to be involved in the processing and storage of emotion memory.

The work was done using a classic training technique in which a mouse in a chamber hears a sound followed by a weak shock that comes through the chamber floor. From then onward, every time the mouse hears the tone, it will assume a crouch position that mice in the wild use to try to hide from predators.

In this study, the scientists identified the neurons that were over-producing CREB when the trained mice heard the tone, and zapped only those neurons using a diphtheria toxin. They then exposed the treated mice to the tone. The mice did not react, suggesting their memory linking it to fear of the shock was erased.

PTSD treatment a possible goal
The scientist whose work in reconsolidating memory — a term which means in essence reworking a memory — inspired Eternal Sunshine of the Spotless Mind said Josselyn’s team has found “one of the Holy Grails” of memory work.

“The elegance in this one, which goes orders of magnitude beyond other studies, is that now they didn’t do something that was global to all neurons in the lateral nucleus,” said Karim Nader, a professor of neuroscience at McGill University in Montreal.

“They can kill only the neurons that they think express the memory. And it leaves all the other neurons intact.”

Nader said the work could eventually help scientists figure out how to assist people in overcoming pathological fears caused by the memory of a traumatic event.

But much remains to be done before that could happen. For instance, the technique Josselyn’s team used worked wonderfully in mice, but couldn’t be used in people.

“In humans, one wouldn’t want to kill these neurons. And certainly it’s not feasible to do it by this technology because you’re not going to inject diphtheria … viruses [into people],” said Salter, who is Josselyn’s department head but who was not involved in her work.

“So as a therapeutic strategy, this isn’t going to be it. But the idea is then to use this as a step forward and then to go on to come up with strategies that could then be used.”

Salter said it is conceivable that the storage system for fear-based memories that’s at work in a mouse brain is similar to the system by which fear memory is stored in human brains.

“Many of these biochemical pathways are conserved all the way from fruit flies up into humans,” he said. “So I think that’s the tack, is to try to find commonalities and take advantage of those commonalities.”

Salter said in building on this and other work, scientists may figure out a way to manipulate fear memories so that excessive fear is toned down, but the memory itself is not erased.