In the 1990’s, Todd Sacktor, neurologist and molecular biologist at the State University of New York Downstate Medical Center, discovered that PKmZeta, persistently expressed and found only in the brain, was the enzyme implicated in the formation of memory. “Basically, I guessed! But it was an educated guest,” he says. Inspired by one of his professors from Columbia University, Sacktor tested PKmZeta on hippocampus slices and it came out to be necessary and sufficient to the formation of memory. More than 15 years of work after, he proved that he was right in live animals. He erased some rats’ memory by inhibiting the role of that specific enzyme.

To prove his hypothesis on live animals, Sacktor had them learned a simple task he knew would be stored in their hippocampus. He trained some rats to avoid a shock zone on a rotating platform. The rats were placed on a slowly spinning circle. One portion of the space was declared the “shock zone” and remained stationary while the rest spun. So the rats had to keep moving to avoid being eventually thrown into the shock zone due to the platform rotation. One day to one month after they learned the task, some rats received an injection of a chemical dubbed ZIP into the hippocampus. While “control animals” who had not receive any injection remembered which areas of their environment to avoid, “inhibitor-injected” animals explored the entire environment, appearing to have no memory of previous training.

To get a glimpse of what happened one needs to understand how the gap between two neurons, named the synapse, works. In the brain, neurons spread their tentacles, the axons and the dendrites, to connect to each other. At each connection, the pre-gap side releases some messenger, the neurotransmitters, and on the post-gap side, a receptor traps those transmitters to treat their message. The receptors are floating in and out of the synapse. But when a memory is formed, PkmZeta doubles their number by trapping them for a longer period of time inside the synapse. More transmitters can get trapped and as a consequence, it enhances the strength of the connection between the neurons.

Unlike any other enzyme in the body, PKmZeta action is permanent. Meaning that once it gets activated, it never stop working. To stop its action and erase the memory out of the rats’ brains, Sacktor injected an artificial key, the ZIP drug, to lock the PKmZeta action. The level of receptors went back to normal and the connection between the neurons got weaker. And the ZIP effect was persistent. “What’s remarkable, is that the memory never comes back,” Sacktor says.

However, if the rats were retrained after the drug was eliminated from their bodies, they could learn the task again. “We haven’t damaged the brain or even functionally impaired memory other than wiping out previous long-term memory,” Sacktor explains. Applied to humans, those results could lead to treatments for post-traumatic stress disorders. A doctor could inject a drug in the specific zone of the brain activated by fears. The product would inhibit the action of the protein PmZeta that wakes up every time the memory comes back.

But Dr. David Caplan, neurologist at the Massachsetts General Hospital, doubts that those kinds of treatments could help patients in a foreseeable future and is deeply convinced that the injected drug could also damage other parts of the brain. “Our brain is filled with memories that sometimes we can’t access. Think about them as if they were recorded on videotape. The play head of our brain, the temper lob, is very fragile. I am sure it is today, totally impossible [to erase memory] without damaging the play head of our brain,” he explains over the phone.

Sacktor agrees that his research is not precise enough to erase and pinpoint one specific memory. Right now, the only selectivity has to do with brain anatomy. He can only inject the ZIP drug into a particular part of the brain, and erase all the memories stored there. But he is more optimistic than Caplan as to the future applications of his work in treating humans.