Making mouse memories

Neuroscientists create a synthetic recollection of fear in rodents

In the movie Eternal Sunshine of the Spotless Mind, scientists erase troubling memories from Jim Carrey’s head. In real life, scientists have done the opposite.

By reactivating certain nerve cells, researchers make artificial memories pop into mice’s heads. The results, published in the March 23 Science and online March 22 in Nature, offer a deeper understanding of how the brain creates and uses memories.

Much of what scientists know about how the brain remembers comes from studies that look for signs of natural memories in the brain or that disrupt memories. In the new work, memories are actually created, says neuroscientist Richard Morris of the University of Edinburgh in Scotland. “To my mind, this is an extremely important step forward,” he says.

Though the two teams used different approaches, they both created a false memory of a fearful situation in mice. In the work reported in Science, neuroscientist Mark Mayford and colleagues relied on a molecule that, upon binding a particular drug, could activate nerve cells. The team genetically engineered the mice so that only the nerve cells active during the formation of a particular memory would make the molecule. In a sense, this molecule acts as a trail of bread crumbs in a forest, marking cells in the brain that make a memory and allowing scientists to reactivate those cells later.

The marked memory was of a square room with opaque white walls and floor, and no particular odors. The mice played in this room, had their memory tagged and later went into a different room — this time, a wintergreen-scented room with a black-and-white checkered wall and a gridded floor. Here, the animals were subjected to shocks. After a while, the animals learned to freeze in response to being in the room.

In some of the trials, the researchers reactivated the memory of the white room during the shock session. This taught the mouse to associate the combination of the reactivated memory and the scented room with a shock, forming a hybrid memory. Sure enough, in later trials, these mice froze only when researchers placed the mice in the second room and simultaneously reactivated the artificial memory. “We’ve essentially created a synthetic memory,” says Mayford of the Scripps Research Institute and the University of California, San Diego in La Jolla.

Of course, no one knows what the experience was like for the mice. But the data suggest that rather than toggling back and forth, the sensation would be more like a hybrid between the two places.

The study in Nature, led by Susumu Tonegawa of MIT, labeled and recreated a fearful memory in mice using molecules that respond to certain kinds of light, a technique called optogenetics. A day after the fearful experience, in an entirely different room, the animals froze in fear when the light was turned on and the artificial memory was called to mind. This flash of light “led to the entire recall of yesterday’s terrible experience,” says Tonegawa. Minutes later when the light was turned off, the mice moved normally.

The results are “a dramatic way to demonstrate that behavior is actually based on very specific changes in the brain,” Tonegawa says. Stimulating a small number of nerve cells led to a complex behavioral response.

Compared to what the mouse’s brain normally does to call up a memory, these artificial reconstructions are crude. “We were surprised that it didn’t make a mess out of the animal, and that the mouse could use it at all,” Mayford says.

Laura Sanders

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

More Stories from Science News on Life

From the Nature Index

Paid Content