From The Quarterly, Winter 2014

It is well known that memories are consolidated and strengthened during sleep. 2010 NARSAD Young Investigator Grantee Asya Rolls, Ph.D., and colleagues at Stanford University, have shown that memories can also be weakened during sleep. They are using this finding as the basis for a potential new approach to alleviating symptoms of post-traumatic stress disorder (PTSD) and other psychiatric disorders involving painful memories. The team reported results of its experiments in a paper titled “Sleep To Forget: Interference of Fear Memories During Sleep,” published October 1, 2013 in the journal Molecular Psychiatry.

Many of the commonly used treatments for PTSD and other disorders triggered by traumatic or painful memories seek to modify the response to such memories, to render them harmless or less likely to cause pain, through a method called extinction therapy. To achieve memory extinction, the patient must first recall the traumatic event while in a safe environment such as a therapist’s office, and then learn to make new, safe associations with the memory, thus de-activating it as a fear trigger.

Because extinction therapy has the disadvantage of making the patient remember, and to varying extents, relive the original trauma, Dr. Rolls and team, working in the laboratory of Craig Heller, Ph.D. and Luis de Lecea, Ph.D., had the novel idea of manipulating the memories during sleep rather than during wakefulness. For their experiments, they used mice conditioned to feel fearful when exposed to a frightening cue––in this case a jasmine odor––to see whether the fear memory could be weakened while the animals were asleep.

The researchers succeeded in both strengthening the fear memory, and in an accompanying set of experiments, weakening it. They accomplished the latter by taking the mice already conditioned to experience fear when the odor was introduced in their cage and then treating them with protein synthesis inhibitor, or PSI, a substance that blocks natural processes that build new proteins. PSI was injected into a portion of the amygdala, a brain area known to be central in the processing of fear memories. The animals’ subsequent behavioral responses indicated that the fear memory was weakened.

These findings demonstrate that specific fear memories can be selectively reactivated and either strengthened or attenuated during sleep, suggesting the potential for developing new, promising sleep therapies for human emotional disorders. Among the benefits that might result from therapies based on Dr. Rolls’ investigations is that patients would not have to re-experience fear in order to defuse it.

“We see this as proof of concept that memories can be manipulated during s leep a nd that su ch manip ul ation offers diverse therapeutic potential,” Dr. Rolls says, but, she cautions, “we must remember that th ere i s still a long way to go until such therapy can be applied to humans. There are many challenges ahead.”