Implanting False Episodic Memories in Mice

Neuroscientists at MIT have shown that they can plant false memories in the brains of mice. False memory is something that has been well-documented.

There have been many court cases where defendants have been found guilty based on testimony from witnesses and victims who were sure of their recollections, but DNA evidence later overturned the conviction. In a paper describing the findings, researchers noted that many of the neurological traces of these memories are identical in nature to those of authentic memories.

“Whether it’s a false or genuine memory, the brain’s neural mechanism underlying the recall of the memory is the same,” said senior author Susumu Tonegawa.

The study also provides more evidence that memories are stored in networks of neurons forming memory traces for each experience we have.

Optogenetics and Engrams

Neuroscience has long looked for the location of these memory traces, also called engrams. In the pair of studies, Tonegawa’s team demonstrated that they could spot the cells that make up part of an engram for a specific memory and reactivate it using a technology called optogenetics.

Episodic memories, in other words memories of experiences, are composed of associations of several elements, including objects, space and time. These associations are encoded by chemical and physical changes in neurons, as well as by modifications to the connections between the neurons. But just where these engrams are located in the brain has been an enduring question in neuroscience.

“Is the information spread out in various parts of the brain, or is there a particular area of the brain in which this type of memory is stored? This has been a very fundamental question,” Tonegawa says.

Canadian neurosurgeon Wilder Penfield suggested in the 1940s that episodic memories are located in the brain’s temporal lobe. When Penfield electrically stimulated cells in the temporal lobes of patients who were about to undergo surgery to treat epileptic seizures, the patients reported that specific memories popped into mind.

Later studies of the amnesiac patient known as “H.M.” confirmed that the temporal lobe, including the area known as the hippocampus, is critical for forming episodic memories.

Hippocampus Cells and Channelrhodopsin

But these studies did not actually prove that engrams are stored in the hippocampus, Tonegawa says. To prove that, researchers had to show that activating specific groups of hippocampal cells is sufficient to produce and recall memories.

And so, Tonegawa’s lab turned to optogenetics, a new technology that allows cells to be selectively turned on or off using light.

For this pair of studies, the researchers engineered mouse hippocampal cells to express the gene for channelrhodopsin, a protein which activates neurons when stimulated by light. They also modified the gene so that channelrhodopsin would be produced whenever the c-fos gene, necessary for memory formation, was turned on.

In a study last year, the researchers conditioned these mice to fear a particular chamber by delivering a mild electric shock. As this memory was formed, the c-fos gene was turned on, along with the engineered channelrhodopsin gene. This way, cells encoding the memory trace were “labeled” with light-sensitive proteins.

The next day, when the mice were put in a different chamber they had never seen before, they behaved normally. However, when the researchers delivered a pulse of light to the hippocampus, stimulating the memory cells labeled with channelrhodopsin, the mice froze in fear as the previous day’s memory was reactivated.

Fear of Memories

“Compared to most studies that treat the brain as a black box while trying to access it from the outside in, this is like we are trying to study the brain from the inside out,” said co-author Xu Liu. “The technology we developed for this study allows us to fine-dissect and even potentially tinker with the memory process by directly controlling the brain cells.”

To explore whether they could use these reactivated engrams to plant false memories in the mice’s brains, researchers placed the mice in chamber, A, but did not deliver any shocks. As the mice investigated the chamber, their memory cells were labeled with channelrhodopsin.

The next day, the mice were placed in a second, disimilar chamber, B. After a while, the mice were given a mild foot shock. At the same time, the researchers used light to activate the cells encoding the memory of chamber A.

The mice on day 3 were placed back into chamber A, where they now froze in fear, even though they had never been shocked there. A false memory had been implanted: The mice feared the memory of chamber A because when the shock was given in chamber B, they were reliving the memory of being in chamber A.

Furthermore, the false memory seemed to compete with a genuine memory of chamber B, the researchers found. These mice also froze when placed in chamber B, but not as much as mice that had received a shock in chamber B without having the chamber A memory activated.

Immediately after recall of the false memory, researchers then showed, levels of neural activity were also elevated in the amygdala, a fear center in the brain, just as they are when the mice recall a genuine memory.


Steve Ramirez, Xu Liu, Pei-Ann Lin, Junghyup Suh, Michele Pignatelli, Roger L. Redondo, Tomás J. Ryan, and Susumu Tonegawa.
Creating a False Memory in the Hippocampus.
Science, 26 July 2013: 387-391 DOI:10.1126/science.1239073

Photo credit: Steve Ramirez and Xu Liu Shows cells (highlighted in red) where memory traces are stored in the mouse hippocampus.

 

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