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A flash of light implants false memories in mice

Researchers alter rodents' recollections by exciting just a few neurons

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Just a tiny fraction of the brain’s neurons firing at the wrong time may be able to make a figment of the imagination seem real. Scientists have come to that conclusion after implanting false memories into the brains of mice.

“It’s fairly astounding,” says neurobiologist Mark Mayford of the Scripps Research Institute in La Jolla, Calif, who was not involved in the research. “Stimulating a small amount of cells can put a thought into an animal’s head.”

Neurobiologists have known for years that the hippocampus, a seahorse-shaped region deep in the brain, plays a role in learning and memory. And countless studies have shown that when it comes to recalling events, humans tend to make mistakes. (Of the first 250 prisoners exonerated in the United States based on DNA evidence, some three-quarters were originally convicted at least in part because of faulty eyewitness testimony.)

But exactly how neurons in the hippocampus harbor and retrieve memories — and where they go wrong — has been difficult to understand without observing an example in animals, says Susumu Tonegawa, a neuroscientist at MIT.

To understand how neurons create memories, Tonegawa and his colleagues used optogenetics. In the relatively new technique, researchers implant tiny optical fibers in the brains of living animals. The fibers deliver pulses of light directly to neurons that have been genetically engineered to react to the flashes.

In previous work, the researchers engineered mice with neurons that are sensitive to blue light — but only when a gene that turns on during new experiences is active. The team then showed that flashing the neurons with light alone forced a previously created memory of a new experience to pop into a mouse's head (SN: 4/21/12, p. 10).

Neurons in a small region of the hippocampus called the dentate gyrus were particularly adept at triggering memories this way.

For the new study, Tonegawa’s team tested if neurons in the dentate gyrus could create a memory of an event that never happened. The researchers allowed the mice to explore a new cage, switching on their memory-forming neurons.

The mice then entered a second cage where they received a series of mild electric shocks on their feet, making them fear the new place. At the same time, the researchers delivered pulses of blue light to the animals’ brains to conjure up memories of the first cage. When back in the safe environment of the first cage, the animals froze in fear even though nothing upsetting had ever occurred there.

The false memories could be produced by stimulating just 3 percent of the cells in the dentate gyrus — about 30,000 cells, the team reports in the July 26 Science. “It is really surprising that these things can be done by stimulating this relatively small amount of cells,” Tonegawa says. The researchers don’t know the smallest number of cells capable of making a memory.

Tonegawa says pleasurable experiences likely alter memories just as much as fearful ones do. The team is testing that hypothesis by looking at how memories change when male mice spend time with females.

The study could help scientists understand false memories in humans, Tonegawa says, but the jumble of memories stored in the human brain is likely more complex than that of a caged mouse. Along with the evolution of higher thought and imagination, Tonegawa says, came the ability of the human mind to create elaborate memories, some of which are false.

“This tendency to form false memories would probably increase as animals evolved from rodent to monkey to human,” Tonegawa says. “Without this very rich mind activity which allows us to be a creative species, we wouldn’t have art or culture. But we’re paying a tax for it.”

Editor's Note: This story was updated on August 7, 2013, to clarify the distinction between the previous study and the new one.

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