The best way to forget an alarming memory, oddly, is to remember it first. That’s why the 7 percent of American adults who experience post-traumatic stress disorder (or PTSD) at some point in their lives are often asked by therapists to recall the incident that taught them the fear in the first place.
Stirring up a memory makes it a little unstable, and for a window of perhaps three hours, it’s possible to modify it before it settles down again, or “reconsolidates,” in the brain. Reliving traumatic moments over and over in safe conditions can help a person unlearn the automatic feeling of alarm.
The trouble is that “fear extinction” therapy, as researchers call it, works well with recent memories but not so well with deeply entrenched, long-term horrors. But a new study in mice, from the laboratory of fear memory researcher Li-Huei Tsai of MIT, now promises to change that.
The scientists, who reported the study in Cell, taught lab mice fear by the standard method of applying a mild electric shock, accompanied by a loud beep. Mice show fear by freezing in place, and they quickly learned to freeze when they were put in the test box or heard the beep. It was a “conditioned response,” like Ivan Pavlov ringing a bell to make dogs salivate, in his pioneering experiments on learning and memory.
For mice, fear extinction therapy meant going back in the test box for a while, but without the shock. That alone was enough to unlearn the conditioned response if it was a new memory, just a day old. But if the mice had been trained 30 days earlier, the therapy didn’t work.
So Tsai and lead author Johannes Gräff combined the extinction therapy with a type of drug that has recently shown promise in mice as a way to improve thinking and memory. HDAC inhibitors (that is, histone deacetylase inhibitors) boost the activity of genes in ways that help brain cells form new connections; new connections are the basis of learning.
The HDAC inhibitors alone had no effect, but drugs and therapy together seemed to open up and reconnect the neurons where long-term traumatic memory had until then been locked away. Mice could be taught to overcome the entire conditioned response or just a part—ignoring the beep, for instance, but still freezing in the test box.
Getting from mice to humans is, of course, always a great leap. But the U.S. Food and Drug Administration has already approved investigative use of some HDAC inhibitors for certain cancers and inflammatory disorders, which could make it easier, Gräff speculates, to get to clinical testing for human psychiatric therapy.
Marie Monfils, who studies fear memory at the University of Texas at Austin, calls the new study “beautifully done,” with potential to “open up really interesting avenues for research and treatment.” That could be big news for a society alarmed by the surge in military suicides and other PTSD-related problems from more than a decade of war. For the desperate patients themselves, science now holds out hope that it will soon be possible, in effect, to rewind memory to a time before trauma stole their peace of mind.