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To sleep, perchance to forget fears

A Eunuch's Dream by Jean-Jules-Antoine Lecomte du Nouÿ, via Wikimedia Commons

Traumatic memories can be manipulated in sleeping mice to reduce their fearful responses during waking hours.  The finding, announced by  Stanford University researchers at the Society for Neuroscience meeting in New Orleans, Louisiana, suggests that sleep-based therapies could provide new options for treating conditions such as post-traumatic stress disorder (PTSD).

“We have an ethical obligation to study this because PTSD is so hard to treat,” says Daniela Schiller of Mt. Sinai School of Medicine, who studies the human neurobiology of fear and was not involved in the study. “It’s definitely promising,” she says.

Currently, one of the most common treatments for PTSD requires the patient to recall the original trauma — an explosion, for example — in a psychiatrist’s office. With repeated ‘safe’ exposures to the memory, patients may learn new associations that reduce the power of loud noises and other cues to trigger flashbacks.

Some patients are daunted by the task of intentionally recalling their traumatic memories. And many patients who undergo the therapy eventually relapse, says lead author Asya Rolls, perhaps because the technique becomes strongly associated with the psychiatrist’s office and does not generalize well to the outside world.

As an alternative to this approach, Roll and her colleagues looked to emerging research that suggests sleep may be a unique new setting in which to manipulate memories.

In the study, they trained mice to fear the smell of jasmine by repeatedly pairing puffs of the chemical amyl acetate with weak electric shocks delivered to the mice’s feet. After 24 hours, the mice would freeze — a classic fear response — upon smelling the chemical alone.

Some mice received conventional exposure therapy, experiencing repeated odor puffs without ensuing electric shocks. These mice overcame their fear responses a day later, but relapsed when placed in a new cage — one not associated with the therapy.

In other mice, Rolls administered a drug to block protein production in the basolateral amygdala — a brain area associated with storage of fearful memories — just before the animals went to sleep. The researchers then exposed the sleeping mice to repeated odor puffs alone. Upon waking, these animals showed reduced fear responses to amyl acetate that carried over even into new environments.

“I think it’s actually causing a reactivation of the same neurons that encoded the information during wakefulness,” says Gina Poe, a sleep researcher at the University of Michigan. She suspects that the protein synthesis drug “doesn’t allow the memory to be re-stored in the same way as it was before.”

Rolls points out that the protein synthesis drug would not be safe for use in humans, but that existing anti-anxiety medications could potentially have similar effects when paired with sleep-based exposure therapy. Future tests will be needed to uncover the cellular mechanisms of the treatment, but Rolls calls the work a successful proof of concept.

“The idea that you can actually erase memories during sleep, that you can manipulate them,” says Rolls. “It’s exciting.”


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