Scientists Trace Memories of Things That Never Happened
Published: July 25, 2013

The vagaries of human memory are notorious. A friend insists you were at your
15th class reunion when you know it was your 10th. You distinctly remember
that another friend was at your wedding, until she reminds you that you didn’t
invite her. Or, more seriously, an eyewitness misidentifies the perpetrator of a
terrible crime.

Not only are false, or mistaken, memories common in normal life, but
researchers have found it relatively easy to generate false memories
of words and images in human subjects. But exactly what goes on in
the brain when mistaken memories are formed has remained

Now scientists at the Riken-M.I.T. Center for Neural Circuit Genetics at the
Massachusetts Institute of Technology say they have created a false memory in
a mouse, providing detailed clues to how such memories may form in human

Steve Ramirez, Xu Liu and other scientists, led by Susumu Tonegawa, reported
Thursday in the journal Science that they caused mice to remember being
shocked in one location, when in reality the electric shock was delivered in a
completely different location.

The finding, said Dr. Tonegawa, a Nobel laureate for his work in immunology,
and founder of the Picower Institute for Learning and Memory, of which the
center is a part, is yet another cautionary reminder of how unreliable memory
can be in mice and humans. It adds to evidence he and others first presented
last year in the journal Nature that the physical trace of a specific memory can
be identified in a group of brain cells as it forms, and activated later by
stimulating those same cells.

Although mice are not people, the basic mechanisms of memory formation in
mammals are evolutionarily ancient, said Edvard I. Moser, a neuroscientist at
the Norwegian University of Science and Technology, who studies spatial
memory and navigation and was not part of Dr. Tonegawa’s team.

At this level of brain activity, he said, “the difference between a mouse and a
human is quite small.” In both,
memories form in an area of the
hippocampus called the dentate gyrus.

“What I find fascinating about this,” Dr. Moser said, “is that you actually can
point to a physical substrate to memory,” what the researchers call an
Neuroscientists have long talked about engrams, but Dr. Moser said
the recent research is the closest they have gotten to pointing to a spot in the
brain and saying, “That is the memory.”

In the research reported Thursday, Dr. Tonegawa’s team first put mice in one
environment and let them get used to it and remember it. They identified and
chemically labeled the cells in the animals’ brains where that memory was being
formed. The mice were not shocked in that environment.

A day later, in a completely different environment, the researchers delivered an
electric shock to the mice at the same time that they stimulated the previously
identified brain cells to trigger the earlier memory.

On the third day, the mice were reintroduced to the first environment.
They froze in fear, a typical and well studied mouse behavior, indicating
they remembered being shocked in the first environment, something
that never happened
. The researchers ran numerous variations of the
experiment to confirm that they were in fact seeing the mice acting on a false

The tools of optogenetics, which are transforming neuroscience, were used to
locate and chemically label neurons, as well as make them susceptible to
activation by blue light transmitted by a fiber optic cable. With these techniques
the researchers were able to identify and label which neurons were involved in
forming the initial memory of the first environment, and to reactivate the labeled
cells a day later with light.

Dr. Tonegawa said that because the mechanisms of memory formation are
almost certainly similar in mice and humans, part of the importance of the
research is “to make people realize even more than before how unreliable
human memory is,” particularly in criminal cases when so much is at stake.

That unreliability, he said, prompts a question about evolution: “Why is our
brain made in such a way that we form false memories?”

No one knows, he said, but he wonders if it has to do with the creativity that
allows humans to envision possible events and combinations of real and
imagined events in great detail. That rich internal experience fuels work in the
arts and sciences and other creative activities, he said. “Unless you have that
kind of ability, there is no civilization,” he said.

But it could also provide raw material for false memories — a possible “tradeoff
for this tremendous benefit.”
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25 July 2013
Scientists can implant false memories into mice
By Melissa Hogenboom
Science reporter, BBC News

Optical fibres implanted in a mouse's brain activated memory forming cells

A team was able to make the mice wrongly associate a benign environment with
a previous unpleasant experience from different surroundings.

The researchers conditioned a network of neurons to respond to light, making
the mice recall the unpleasant environment.

Reporting in Science, they say it could one day shed light into how false
memories occur in humans.

The brains of genetically engineered mice were implanted with optic fibres in
order to deliver pulses of light to their brain. Known as optogenetics, this
technique is able to make individual neurons respond to light.

Unreliable memory
Continue reading the main story

Start Quote

Our memory changes every single time it's being recorded. That's why we can
incorporate new information into old memories and this is how a false memory
can form...”

Dr Xu Liu
Massachusetts Institute of Technology
Just like in mice, our memories are stored in collections of cells, and when
events are recalled we reconstruct parts of these cells - almost like re-
assembling small pieces of a puzzle.

It has been well documented that human memory is highly unreliable, first
highlighted by a study on eyewitness testimonies in the 70s. Simple changes in
how a question was asked could influence the memory a witness had of an
event such as a car crash.

When this was brought to public attention, eyewitness testimonies alone were
no longer used as evidence in court. Many people wrongly convicted on
memory statements were later exonerated by DNA evidence.

Xu Liu of the Massachusetts Institute of Technology and one the lead authors
of the study, said that when mice recalled a false memory, it was
indistinguishable from the real memory in the way it drove a fear response in
the memory forming cells of a mouse's brain.

Continue reading the main story
How a memory was implanted in a mouse

This cartoon explains how Dr Tonegawa's team created a false memory in the
brain of mice
A mouse was put in one environment (blue box) and the brain cells encoding
memory were labelled in this environment (white circles)
These cells were then made responsive to light
The animal was placed in a different environment (the red box) and light was
delivered into the brain to activate these labelled 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 the mouse was put back into the first environment, it showed
behavioural signs of fear, indicating it had formed a false fear memory for the
first environment, where it was never shocked in reality
The mouse is the closest animal scientists can easily use to analyse the brain,
as though simpler, its structure and basic circuitry is very similar to the human

Studying neurons in a mouse's brain could therefore help scientists further
understand how similar structures in the human brain work.

"In the English language there are only 26 letters, but the combinations of
letters make unlimited words and sentences, this is also true for memories," Dr
Liu told BBC News.

Evolving memories
"There are so many brain cells and for each individual memory, different
combinations of small populations of cells are activated."

These differing combinations of cells could partly explain why memories are not
static like a photograph, but constantly evolving, he added.

Continue reading the main story
Erasing memories?

Brain artwork
Mice have previously been trained to believe they were somewhere else, "a bit
like the feeling of deja-vu we sometimes get", said Rosamund Langson from
Dundee University.

A possibility in the future is erasing memories, she told BBC News.

"Episodic memories - such as those for traumatic experiences - are distributed
in neurons throughout the brain, and in order to make memory erasure a safe
and useful tool, we must understand how the different components of each
memory are put together.

"You may want to erase someone's memory for a traumatic event that
happened in their home, but you certainly do not want to erase their memory
for how to find their way around their home."

"If you want to grab a specific memory you have to get down into the cell level.
Every time we think we remember something, we could also be making changes
to that memory - sometimes we realise sometimes we don't," Dr Liu explained.

"Our memory changes every single time it's being 'recorded'. That's why we can
incorporate new information into old memories and this is how a false memory
can form without us realising it."

Susumu Tonegawa of the Massachusetts Institute of Technology said his
teams' work provided the first animal model in which false and genuine
memories could be investigated in the cells which store memories, called
engram-bearing cells.

"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."

Silencing fear
Neil Burgess from University College London, who was not involved with the
work, told BBC News the study was an "impressive example" of creating a
fearful response in an environment where nothing fearful happened.

"One day this type of knowledge may help scientists to understand how to
remove or reduce the fearful associations experienced by people with
conditions like post traumatic stress disorder."

But he added that it's only an advance in "basic neuroscience" and that these
methods could not be directly applied to humans for many years.

"But basic science always helps in the end, and it may be possible, one day, to
use similar techniques to silence neurons causing the association to fear."

'Diseases of thought'
Mark Mayford of the Scripps Research Institute in San Diego, US, said: "The
question is, how does the brain change with experience? That's the heart of
everything the brain does.

He explained that work like this could one day further help us to understand the
structure of our thoughts and the cells involved.

"Then one can begin to look at those brain circuits, see how they change, and
hopefully find the areas or mechanisms that change with learning."

"The implications are potentially interventions for diseases of thought such as
schizophrenia. You cannot approach schizophrenia unless you know how a
perception is put together."

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