Fake memories have been created in sleeping mice, according to a study published today. The findings suggest that similar techniques could one day be used to treat conditions like post-traumatic stress disorder (PTSD) in humans, though major hurdles remain.
The study, published in the journal Nature Neuroscience, involved five mice that were placed within an enclosed circular space. Researchers used electrical brain implants to create a "reward" sensation in the mice whenever they thought about a specific area of the space during sleep. When they woke up and returned to the space, they went immediately to the area associated with the reward, suggesting that an artificial memory had been formed.
"Learning during sleep has always been a dream."
Previous studies have demonstrated that memories can be both created and manipulated in mice, but the findings published today are the first to show that this can be done during sleep, adding a new wrinkle to the long history of sleep-learning experiments.
"Learning during sleep has always been a dream — no joke intended," says Karim Benchenane, a researcher at the Centre National de la recherche scientifique and one of the study’s co-authors. He notes that in this study, the area of the circular space was never associated with a reward while the mice were awake, meaning that "the only way they could learn is during sleep."
A dozen mice were fitted with electrical implants and placed in a circular, one-meter-wide place, according to the study. The electrical implants allowed the authors to identify the specific brain cells that were activated when the mice entered a particular area of the space. Not just that, though — for five of the mice, the implants automatically stimulated the reward pathways of their brains whenever the cells spiked during sleep. The activated cells are known as place cells because they create a cognitive map of physical spaces, acting as a sort of GPS for the brain. When the mice awoke after receiving the "reward" stimulation and entered the same space, they immediately went to the location associated with the reward. They also spent more than four times longer there than they did the first time they explored the space. Another group of five mice demonstrated similar behavior after receiving the stimulation while they were awake. The other two received no stimulation at all, and demonstrated no association with the reward placement.
"something we've all believed, but which has not really been proven."
The findings mark an important development for the study of spatial memory, as well. Place cells were first identified in 1971 by John O’Keefe, who was honored for his discovery with last year's Nobel Prize in Medicine. It's been widely assumed that place cells reactivate during sleep as a way to consolidate an animal’s memory of certain environments. Today's study is the first to demonstrate this phenomenon in action, proving that when activated during sleep, place cells convey the same spatial information they do when animals are awake.
"It now provides a really clear demonstration of something we've all believed, but which has not really been proven," says Kate Jeffery, a professor of behavioral neuroscience at University College London who was not involved in the study. "Now we know that that’s really the case."
Benchenane acknowledges that the study’s sample size is small, though the complexity of the task involved — going to a specific area of a relatively large pen — all but eliminates the possibility that his team's results are due to chance, he says.
Findings may have implications for PTSD sufferers
One implication of the study may bring hope to PTSD sufferers, says Benchenane, who also heads the Memory, Oscillation and Brain States team at the Ecole Supérieure de Physique et de Chimie Industrielles (EPSCI) in Paris. People with PTSD often feel fearful and stressed, after a traumatic event changes their flight-or-fight response. Though it’s popularly associated with war, it can also be triggered by other events, including muggings, rapes, and natural disasters, according to the US National Institute of Mental Health. But if scientists can manipulate traumatic memories during sleep, it may be possible to make them less harmful to people, perhaps by manipulating traumatic memories while patients sleep so they aren't quite so bad. But that would require a precise and less invasive method of recording neural activity, which doesn’t exist today.
"Now that we’re more sure that memories are being reactivated after they’re formed, and that you can change them, there’s the possibility that we can use that in a therapeutic setting," Jeffery says. "But obviously we’re not going to be sticking electrodes in the median forebrain bundles of humans, so maybe we can do it another way."
Ideally, scientists would be able to identify the precise moment a person thinks of a traumatic experience during sleep, and stimulate the brain to associate that memory with positive feelings. But it’s impossible to say how the human brain would respond to that in practice.
"What you want is for the negative part to be replaced by the positive part," Benchenane says. "But you don’t want the two to be additive, because otherwise you will want something that will scare you, or the positive may become a negative. So we need a little more knowledge about how the positive and negative parts balance in the brain."