Research in mice reveals a new approach to wiping memories from the brain, demonstrating that specific memories can be weakened or strengthened

This article is more than 3 years old

This article is more than 3 years old

The eternal sunshine of a spotless mind has come one step closer, say researchers working on methods to erase memories of fear.

The latest study, carried out in mice, unpicks why certain sounds can stir alarming memories, and reveals a new approach to wiping such memories from the brain.

The researchers say the findings could be used to either weaken or strengthen particular memories while leaving others unchanged. That, they say, could potentially be used to help those with cognitive decline or post-traumatic stress disorder by removing fearful memories while retaining useful ones, such as the sound of a dog’s bark.

“We can use same approach to selectively manipulate only the pathological fear memory while preserving all other adaptive fear memories which are necessary for our daily lives,” said Jun-Hyeong Cho, co-author of the research from the University of California, Riverside.



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The research is the latest in a string of studies looking at ways to erase unpleasant memories, with previous work by scientists exploring techniques ranging from brain scans and AI to the use of drugs.

Published in the journal Neuron by Cho and his colleague Woong Bin Kim, the research reveals how the team used genetically modified mice to examine the pathways between the area of the brain involved in processing a particular sound and the area involved in emotional memories, known as the amygdala.

“These mice are special in that we can label or tag specific pathways that convey certain signals to the amygdala, so that we can identify which pathways are really modified as the mice learn to fear a particular sound,” said Cho. “It is like a bundle of phone lines,” he added. “Each phone line conveys certain auditory information to the amygdala.”

In the first part of the experiment the team played both a high pitched and low-pitched tone to mice. But, when the high-pitched sound was played, the researchers also gave the mice a small electric shock to their feet.



When the high-pitched tone was subsequently played on its own, the mice froze in fear; no such response was seen when the alternative, low-pitched, tone was played.

The team then looked to see if there were differences between the high-pitch and low-pitch tone pathways in the brains of the mice, revealing that, among the mice exposed electric shocks, the connections within the “high-pitched” pathway had become stronger, while the other pathway remained unchanged.

The team found that when mice were subsequently repeatedly exposed to high-pitched sounds without the shocks they lost their fear – a process known as fear extinction.

“Fear extinction is the psychological basis of exposure therapy used in [treating] post-traumatic stress disorder,” said Cho. But, he said, “after exposure therapy, for example two weeks, the fear relapses or recurs spontaneously.”

The new research, he adds, offers an explanation: even after fear extinction, the team found the neural pathway for the high-pitched tone remained strengthened in the mice.

“Fear extinction is not an eraser of fear memory ,” said Cho. “It just hides the fear memory transiently.”

But the team discovered that using a technique called optogenetics, it was possible to truly erase the unpleasant memories.

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This technique involved the researchers using a virus to introduce genes into particular neurons in the brains of the mice that were involved in the “high-pitch” pathways.



Once inside the cells, the genes result in the production of proteins which respond to light, allowing researchers to control the activity of the neurons.

Taking mice with the fearful memories, the team exposed the neurons involved in the “high-pitch” pathway to low-frequency light – an approach which weakens the connections between the neurons.



The upshot was that the mice no longer appeared fearful when they heard the high-pitched tone.

“It permanently erases the fear memory,” said Cho. “We no longer see the relapse of fear.”



Peter Giese, professor of neurobiology of mental health at King’s College London, said it was too soon to think of using the research to help those with psychopathologies, saying it would be unethical to use optogenetic techniques on people. “Exactly how this can be applied to humans is a little bit unclear to me,” he said.

Nevertheless, Giese said the study was a big advance, not only in improving understanding of fear extinction, but also highlighting the importance of the strengthening of connections between neurons in forming memories. What’s more, he said, it reveals a way to reverse the process.

“This is a true erasure of the memory,” he said.