image: This cartoon explains how Dr Tonegawa's team created a false memory in the brain of mice. They first put the mouse in one environment (illustrated as the blue box), labeled the brain cells encoding for the memory of this environment (white circles), and made these cells responsive to light. Then they put the animal in a different environment (illustrated as the red box) and delivered light into the brain to activate these labeled cells. This induced the recall of the first environment -- the blue box. While the animal was recalling the first environment, they also received mild foot shocks. Later when we put the animal back into the first environment, it showed behavioral signs of fear, indicating it had formed a false fear memory for the first environment, where it was never shocked in reality. view more
Credit: Collective Next
Researchers at the RIKEN-MIT Center for Neural Circuit Genetics and MIT's Picower Institute for Learning and Memory have implanted false memories into mice, potentially illuminating the mechanisms underlying the human phenomenon of "recalling" experiences that never occurred.
In previous work, the researchers had detected a single memory in the brain, genetically tagged the brain cells housing that memory with a light-sensitive protein, and flickered pulses of light to "turn on" the memory at any given moment. The latest work, to be reported in the journal Science, tinkers with that memory to change its contents—in essence, creating a false memory.
This work in mice may lead to new understanding of how and why humans form false memories.
Our memories are stored in assemblies of neurons, called engram-bearing cells, that can be compared to Legos. When we recall a sequence of events, our brains reconstruct the past from these bricks of data, but the very act of accessing a memory modifies and distorts it. When you add in the influence of external sources, it's not surprising that memory can be notoriously unreliable, yet inaccurate memories can have dire consequences. Almost three-quarters of the first 250 people to be exonerated by DNA evidence in the US were victims of faulty eyewitness testimony.
"Human studies utilizing behavioral and fMRI (functional magnetic resonance imaging) techniques have not been able to delineate the hippocampal subregions and circuits responsible for generating false memories," said study author Susumu Tonegawa, Picower Professor of Biology and Neuroscience and director of the RIKEN-MIT Center for Neural Circuit Genetics. "Our experiments provide the first animal model in which false and genuine memories can be investigated at the memory engram level."
Recreating fear
Dr Tonegawa and his team successfully created a false memory in genetically modified mice by manipulating engram-bearing cells in the hippocampus, a seahorse-shaped part of the brain known to play a role in forming and storing memories of experiences.
The researchers zeroed in on the animals' brain cells that represented the safe environment of a setting, Box A, and programmed those cells to respond to pulses of light. Next, they placed the animals in a completely different environment—Box B—and pulsed light into their brains to reactivate the memory of Box A.
They then gave the animals mild foot shocks, creating a negative association between the light-reactivated memory of Box A and the foot shocks, which mice find highly aversive.
When the animals were placed back in Box A—the safe environment in which nothing averse had ever happened—the researchers found that the animals now displayed heightened fear responses. In addition, after placing the animals in yet another new environment while shining light on the hippocampal cells that had been artificially associated with fear, the researchers found they could reactivate the false fear memory at will.
"Humans are highly imaginative animals. Just like our mice, an aversive or appetitive event could be associated with a past experience one may happen to have in mind at that moment, hence a false memory is formed," said Tonegawa.
"Remarkably, the recall of this false memory recruited the same fear centers that natural fear memory recall recruits, such as the amygdala," said Xu Liu, a post-doctoral fellow and co-first author of the study. The recall of this false memory drove an active fear response in associated parts of the brain, making it indistinguishable from a real memory. "In a sense, to the animal, the false memory seems to have felt like a 'real' memory," he said.
These kinds of experiments show us just how reconstructive the process of memory actually is," said Steve Ramirez, a graduate student in the Tonegawa lab and the lead author of the paper. "Memory is not a carbon copy, but rather a reconstruction, of the world we've experienced. Our hope is that, by proposing a neural explanation for how false memories may be generated, down the line we can use this kind of knowledge to inform, say, a courtroom about just how unreliable things like eyewitness testimony can actually be."
This work was supported by RIKEN Brain Science Institute and the Howard Hughes Medical Institute.
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Juliette Savin
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RIKEN
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Reference
Ramirez et al. "Creating a False Memory in the Hippocampus" Science, 2013
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Journal
Science