With a Pulse of Light, Researchers Turn Bad Memories Into Good Ones

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By Maggie Fox

Ever had a bad breakup ruin your memory of that perfect Caribbean vacation spot? Ever wish you could use that shortcut again if only you could forget the idiot who T-boned your brand-new car there? Well, there’s no immediate hope for you.

But one experiment shows there may be a way to change emotion-laden memories, perhaps offering a new route for therapy for post traumatic stress disorder (PTSD) and other mental disorders.

Researchers have flipped the memories of mice, making them lose their fear of a place where they were shocked, and making them fear a place where they had recently trysted with a female.

The experiment shows there is a clear physical pathway in the brain that connects memories with the emotional weight given to them – and shows it can be disrupted, the researchers report in the journal Nature.

The scientists won’t be turning out perfect soldiers who have no fear of gunfire anytime soon, or even helping people with post-traumatic stress disorder. It was a complicated experiment that required multiple steps to genetically engineer the mice, with no immediate applications for humans.

“We have no intention…to use this kind of technology in order to alter normal, healthy people’s minds."

But it does show what’s possible and it demonstrates a fairly simple mechanism that the brain uses to help animals – including people – classify memories.

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“We have no intention…to use this kind of technology in order to alter normal, healthy people’s minds,” Susumu Tonegawa of the Picower Institute at the Massachusetts Institute of Technology, who led the research, told reporters.

“Hopefully, we can inspire other labs and other groups of people to imagine translating this information into a way that can be applied in humans,” added Roger Redondo, one of the neuroscientists who worked on the study.

Last year, the same team reported they had implanted false memories in mice.

They used a similar technique to find and manipulate the connections in the brain that link the hippocampus – the seat of memories – to the amygdala, the structure where emotions such as fear and pleasure originate.

Image depicts the injection sites and the expression of the viral constructs in the two areas of the brain studied (Dentate Gyrus of the hippocampus and Basolateral Amygdala)Redondo et al.

They had to genetically manipulate the brain cells of the mice so that specific neurons would respond to a pulse of blue laser light. “When blue light is sensed by the molecule, the molecule changes shape,” Redondo said. This allows neurotransmitters to enter the neuron and turn it “on” or “off”.

They used standard conditioning to measure and control the fear or pleasure responses in the mice, administering shocks to their paws for fear, and putting a female mouse into the cage for pleasure. To cue the mice about location, the cage was patterned with either stripes or spots.

As expected, if the mice were shocked while on one side of the arena, they came to fear and avoid that side. And they'd seek out the place they had found the female mouse before.

“Recording memory is not like a plain tape recorder."

What Tonegawa’s team was able to do was to reverse that association – not by switching up the love nest and the shock zone, but by shining blue light on the mice. A mouse that had been trained to fear one side of the area was suddenly attracted to it.

“These animals do not look confused,” Redondo noted. They clearly chose one side or another. “It’s not like they are running around.”

Tonegawa notes there are less high-tech ways to do this. Changing the emotional associations people place with memory is one goal of psychotherapy, for example. And a bad break-up can make that romantic restaurant look very unappealing all of a sudden.

But this experiment demonstrates just where in the brain these associations are made.

Redondo says the team deliberately chose very strong fear and pleasure associations for a clear result. Human emotions—and even mouse emotions -- are not clear-cut off and on responses. “On purpose, we aimed for the extreme ends of the spectrum,” Redondo told NBC News.

And it’s yet another demonstration that memory is unreliable. “Recording memory is not like a plain tape recorder,” Tonegawa said.