Todd Sacktor: Making Memories -- and Selectively Forgetting Them

When Todd Sacktor was 9 years old, he conducted his first memory experiment, telling his younger brother every day to remember being told to remember. It was a bust—the young researcher himself forgot to keep the experiment going. But the fascination stuck. "I always thought memory was the most mysterious area," says the 52-year-old neuroscientist, who heads a lab at SUNY Downstate Medical Center in Brooklyn where he is developing a way to selectively manipulate memories in rats, delicately erasing some but not touching the others.

Todd Sacktor, Neuroscientist, SUNY Downstate, Brooklyn

Sacktor admits such search-and-destroy memory missions have implications "you never could imagine," some of them chilling. He worries about those, but his primary aim is to understand how memory works to help people. Perhaps a memory that causes post-traumatic stress could be wiped out, or memories in Alzheimer's patients might be enhanced. Sacktor thinks the first patients that may be helped are likelier to have motor memory disorders such as focal dystonia, a condition that causes unwanted movement.

Many neuroscientists believe long-term memories are stored when the brain builds new synapses, the communication channels between nerves. Sacktor disagrees. His notion is that memories are maintained by the constant presence of an enzyme called PKMzeta. The idea came to him in 1985 as—bored in the back seat of the family car—he talked shop with his biochemist dad. The elder Sacktor told him about a family of molecules found in abundance in the brain. That inspired Sacktor's discovery of PKMzeta in 1993 and his proof in 2006 of its connection with memory. The challenge, as he sees it, is to turn the enzyme on and off so selectively that only individual memories will be affected.

Sacktor thinks he and the SUNY researchers he works with are getting closer. The key is ZIP, a drug that interferes with PKMzeta. They have discovered that a rat that has learned it will get a light shock if it crosses into one area of a platform can be made to forget its uncomfortable lesson by injecting a tiny amount of ZIP into a certain part of the brain. That a memory could be erased in this way was "totally unexpected," says David Glanzman, a professor of physiological science and neurobiology at the University of California-Los Angeles.

How the human brain stores information—for example, everything Sacktor knows about squash, his favorite sport—is complicated, however. The rules, the best footwear, and his joy at winning are not all organized the same. The circuitry associated with particular memories will have to be pinpointed far more precisely before they can be selectively erased. "Todd has shown that in principle it might be possible to do this," says Glanzman. If so, Alzheimer's patients might one day be among those who won't forget Sacktor's name.