Toronto researchers have been able to do it in traumatized mice
March 13, 2009
Something horrible happens. A child is lost. A bomb goes off. A car goes out of control.
And deep in the brain, in the lateral amygdala region, a scattered set of neurons come to life and begin to vibrate with fear.
Through an ingenious set of experiments, a group of researchers at Toronto's Hospital for Sick Children have not only located these terror-laden brain cells in mice, but erased them – along with the frightening memories they stored.
While our imaginations have long been captivated by the idea of altering memory – to sinister effect in George Orwell's 1984 and poignantly in the film Eternal Sunshine of the Spotless Mind – this research suggests a more therapeutic use.
The study, which appears today in the journal Science, may hold out the hope that terrifying memories one day might be erased before they can fester into such conditions as post-traumatic stress disorder.
While the sights and sounds of a blast or crash would stay intact, the memory of the fear it caused could conceivably be removed, the researchers suggest.
"You wouldn't want to completely get rid of all aspects of a memory," says Dr. Michael Salter, head of the Neurosciences & Mental Health program at the hospital.
"To help people with these kinds of post-traumatic stress disorders ... you might just want to minimize the emotional association between the memory and the highly disruptive and negative emotions that people have in this context."
He says the research may well conjure "Orwellian" notions of thought control, "but that's not really the goal of this. The idea would be (to use it) in a therapeutic way."
Salter was not involved in writing the paper, but was speaking on behalf of senior author Sheena Josselyn, a Sick Kids scientist who politely declined an interview request because she had "just gone into labour." Josselyn and her co-author husband, Paul Frankland, do much of their work in Salter's program.
Salter says the fear-storing neurons found in the mice are almost certainly located in the same amygdala region in human brains and work in much the same way.
The study, he says, suggests that only those amygdala neurons that express high levels of a brain protein known as CREB – about 10 to 20 per cent of the cells in the region – are involved in storing fearful memories.
Known as the universal memory molecule, CREB is essential in allowing brain cells to lay down memories of all kinds.
The researchers were able to selectively stimulate the specific fear-storing neurons by introducing a virus that triggered this CREB and turned the cells on.
After stimulating their CREB-rich cells, the mice were played a tone accompanied by an electrical shock to their feet, establishing a memory of fear to that specific sound in the excited cells.
A second virus was then introduced that migrated specifically to the CREB-expressing neurons and made them susceptible to a diphtheria toxin. When the toxin was injected, it killed the neurons where the fearful memory was stored.
Josselyn stressed in an earlier podcast interview conducted by the journal that the experiment did not destroy the brain's entire capacity to remember fear, only the specific recollection of the shocking tone.
Indeed, when exposed to the same tone and shock combination again, the mice were able to relearn their wariness of the sound.
Injecting diphtheria toxins to kill brain cells in humans would never be an acceptable therapy, Salter says. But there could be medicinal methods to disrupt the natural biochemical pathways that turn on the CREB mechanism and prevent fearful memories from taking root.
The scientist whose work in reconsolidating memory inspired the film Eternal Sunshine of the Spotless Mind said Josselyn's team has found "one of the Holy Grails" of memory work.
"The elegance in this one, which goes orders of magnitude beyond other studies, is that now they didn't do something that was global to all neurons in the lateral nucleus," said Karim Nader, professor of neuroscience at McGill University. "They can kill only the neurons that they think express the memory."
In the film, ex-lovers played by Jim Carrey and Kate Winslet elect to have their memories of each other erased after their relationship sours. Despite the treatment, however, they eventually reunite.
With files from The Canadian Press
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