The idea of implanting memories has been a staple of science fiction for decades, dating back to Philip K. Dick's We Can Remember It for You Wholesale, which became the Arnold Schwarzenegger movie Total Recall. Now researchers are closer to producing false memories in the brains of mice.
The technique could lead to treatments for phobias and post-traumatic stress disorder in humans. "It shows that the stuff from movies like Inception or Total Recall is possible," said graduate student Steve Ramirez, of the RIKEN-MIT Center for Neural Circuit Genetics in Cambridge, Mass. He and his colleagues, led by Susumu Tonegawa, reported their findings in this week's issue of the journal Science.
To give false memories to mice, the researchers started by engineering a benign virus to infiltrate cells and unload a gene that directs the cell to produce a protein called channelrhodopsin-2. From previous studies, the researchers knew that the protein stimulated cellular activity -- in this case, memories -- when exposed to light.
They injected the gene-toting virus into a part of the mouse's brain called the hippocampus. This region is where new memories of day-to-day activities, called episodic memories, form and are stored. The formation and storage of memories occurs when certain proteins in the brain change slightly. Based on research the team did last year, they knew which hippocampal cells to target with light.
To illuminate the cells, the scientists inserted a thread-thin fiber optic cable into the mouse's brain.
Next, they put a mouse into box called environment A and dubbed it the "safe" zone. In this box, the mouse was allowed to move about in a normal way for about 10 minutes. The mouse ran around and explored, acting generally calm.
The next day the scientists put the mouse in another box called environment B. At that point they pulsed light through the fiber optic cable and flashed the brain cells that produced the channelrhodopsin-2 protein. This stimulated a memory. At the same time they gave the animal a mild shock to its feet.
"Here, we were trying to artificially make an association between the light-reactivated memory and the foot shocks. We were just trying to artificially connect the two," Ramirez said.
The next day, they put the mouse back into box A, the safe zone. Instead of behaving normally, though, exploring the box and acting calm, the mouse froze in place or ran into the corner as if were agitated and scared. It seemed to have "remembered" being shocked in box A, even though the negative experience had occurred in box B. When the researchers removed the mouse and put it into a third or fourth box, the mouse behaved calmly. The researchers conducted the same experiment dozens of times on different mice, with similar results.
"They appeared to be recalling being shocked in box A, even though that had never happened," Ramirez said. "A false memory had been formed and recalled."
Jason Snyder, an assistant professor of psychology at the University of British Columbia, who was not involved in the study, said the group's research was interesting because it demonstrated not only where memories go, but also how to modify them. And knowing more about the neurological mechanisms associated with disorders like PTSD could open up avenues for therapy.
For example, a combat veteran suffering from PTSD could be asked to remember a stressful time, while a physician stimulated a part of the hippocampus known to produce more pleasant memories.
Ramirez noted that the technique used on humans would probably not involve a fiber optic cable, since that's invasive. But it could involve some kind of drug-induced stimulation, since there are already a number of drugs that target specific brain regions -- recreational drugs, for instance, target reward centers. The trick would be making one that focused on a protein or receptor unique to the hippocampus.
The experiment also sheds light on how humans form false memories, said Tonegawa. There are some dramatic examples of people suddenly having a memory of a traumatic event, such as childhood sexual abuse. But sometimes whether the memory is true or not becomes controversial. Tonegawa said his team's most recent work provides an animal model of how false memories can appear. Further work needs to be done to show if false memories look different from the real thing.
Readers of more dystopian science fiction might ask if this could be used for mind control. Ramirez said he is conscious of that, even though such an experiment with current technology would never pass muster with an ethics review board. "It's important to be having these conversations now," he said.
Besides the possibility of mind control or psychiatric treatment, Tonegawa said it's also possible that the ability to make false memories is what makes humans as smart as we are. "This is all my speculation, but maybe it has something to do with fact that humans are such imaginative creative animals," he said.