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December 17, 2008

Erasing Memories

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This is not a plot device in the latest thriller, it's real-- scientists have shown that injecting an experimental drug into the brain can completely erase long-term memory in animals. This ScienCentral News video explains how this research could lead to new treatments for those who suffer from painful memories, like people with Post-Traumatic Stress Disorder (PTSD).

Wipe Out

SUNY Downstate Medical Center neurologist Todd Sacktor compares memory to a glue that connects our consciousness. "It's like the essence of what keeps our soul together, our character together," he says. Despite the importance of this powerful, intangible wonder called memory, the mechanics of it still baffles scientists. And Sacktor recently peeled off one layer of the mystery.

Sacktor and his collaborators at the Weizmann Institute of Science in Israel discovered that they could wipe out the long-term memory of rats with a single injection.

"We went out even weeks and weeks later, and still the memory was erased, just like that," says Sacktor, snapping his fingers.

The researchers trained rats to avoid certain tastes in drinks that the animals learned to associate with an upset stomach. Weeks later, they gave the rats an experimental drug called "ZIP" and, within minutes, the animals forgot which drinks to avoid. As Sacktor and his colleagues wrote in the journal "Science," the drug works by blocking a molecule called PKM zeta, which seems crucial to preserving memories.

Memory Motor

PKM zeta molecule
The PKM zeta molecule seems crucial to maintaining memory.
image courtesy of Todd Sacktor
Sacktor says that this molecule works as a continuous memory motor when nerve cells, or neurons, in the brain communicate with each other as memories are formed. It triggers twice the number of receptors from one neuron to accept signals from another. But if that motor gets jammed, the number of receptors gets reduced again and the memories disappear.

"It turns out it's actually very straightforward to jam that little molecular motor and then within minutes, as far as we can tell all of the animals long-term memories just disappear," he says.

In fact, in a study published last year with colleagues at SUNY Downstate Medical Center, Sacktor learned that PKM zeta, when blocked in another area of the brain, wiped out long-term memories in their temporary storage area.

"We're able to erase all of the long term memories and yet keep the short term memories intact," Sacktor says.

The new paper showed that the same molecular motor — PKM zeta — maintains memory in its permanent storage area in the brain. And in another study, he found the molecule caught in the abnormal tangles in brains of Alzheimer's patients, like fish in a net. This may mean that the molecules become deactivated in those with the disease.

"And that could have important clinical applications for how we can make our memories better or if we have very, very disturbing memories, how to eliminate those permanently," Sacktor says.

Continuing Research

Memory researcher Joseph Ledoux of New York University says the study is fascinating, especially because the memories were erased weeks after they were formed. "This is a very powerful molecular technique," says Ledoux. "It's very powerful at the molecular level." But he says that to be used in people, the drug would have to be more precise.

"You don't want to take a patient with PTSD (Post-Traumatic Stress Disorder) and, you know, wipe out their memory. What you want to do is selectively affect the memories that the patient is suffering from," he explains. Ledoux thinks that combining the molecular specificity of Sacktor's technique with the behavioral specificity of his own memory research could lead to treatments for those with PTSD.

This study was published in Science, August 17, 2007
Study co-authors: Reut Shema and Yadin Dudai
Research funding: Todd Sacktor by National Institute of Mental Health; Reut Shema and Yadin Dudai by Israeli Science Foundation

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