Enzyme revives long-term memories

Boosting levels in the brain helps rats remember old times

In “Memory,” a song from the musical Cats, an aging feline invites old memories to live again. Now, that power may be in the hands of the cat’s worst enemy — the rat.

REMEMBER THE TIME Scientists are using viruses to coax brain cells to increase their output of one brain protein — called PKM-zeta — in an effort to boost rat memory. Virus-treated neurons (shown in green) pump out more protein (red), causing these brain cells to glow bright (yellow) under a microscope. Weizmann Institute of Science

Increased levels of one natural brain enzyme supercharge rat memories, a study suggests. And it’s not just new, short-term memories. The enzyme — called PKM-zeta — gives rats better recall of old remembrances, too, a U.S.-Israeli team reports in the March 5 Science.

So far, existing memory boosters mostly help animals like rats store lessons or events more efficiently. It’s a lot harder to give furry critters better recall of memories already sitting in long-term cold storage, says study coauthor Yadin Dudai.

In a number of recent studies, researchers showed that they could make rats forget a range of old learned behaviors by blocking the protein in the brain. Rodents with too little PKM-zeta, for instance, didn’t know to avoid liquids that had made them sick in the past. So Dudai’s team tackled the next big question. “If you, indeed, can block the memory by blocking the enzyme, can you enhance the memory by enhancing the enzyme?” says Dudai, a neurobiologist at the Weizmann Institute of Science in Rehovot, Israel.

Spoiler alert: You can. Dudai’s team injected rats with viruses carrying loads of PKM-zeta–producing genes, shooting the infectious agents right into the wrinkly, outer region of the brain called the neocortex. Cells in the cortex then churned out lots of the protein. The rodents didn’t instantly recall where they left that cheese, though. Researchers trained the rats to associate certain tastes — like sugary or salty — with gross feelings akin to mild food poisoning. Rats that received the enzyme boost remembered to steer clear of those tastes much better than control rats did.

Dudai says what’s really amazing is that the taste training had taken place days before the injections. In other words, the enzymes gave a kick to memorable experiences that had long since gone from short-term to long-term status. “The memory was already there, and the memory was formed normally,” he says. “And then you access the memory and enhance it.”

The results build a rock-solid case for PKM-zeta, says David Glanzman of UCLA, who studies memory in significantly smaller critters, marine snails. Now, researchers need to find out what’s going on, he adds. PKM-zeta seems to be a brain gardener. The enzyme waters and arranges neurons, keeping the connections between these memory-storing cells flowing. Even momentary disruptions to PKM-zeta can obliterate many long-term memories seemingly for good. But whether PKM-zeta works on a general or specific level isn’t clear. “Is it boosting some general process of retrieval?” asks Glanzman. “Or is it specifically enhancing that memory?”

There’s a lot of interest in memory-related medicine, either to jog good memories or — in patients with post-traumatic stress disorder, say — help people forget bad ones, Glanzman says. He’s wary about bringing PKM-zeta into that realm just yet. “You have to know where the memory is in the brain,” he says. “We don’t have a very good way to do that right now.” Without knowing which neurons store which memories, treatments aimed at creating a tabula rasa after trauma could unintentionally make people forget cherished things like their grandmothers, he says. “There’s a reason why the brain keeps memory under tight regulation.”