May/June 2008

Dice-K!

An MIT professor names a brain research tool after a beloved Red Sox pitcher.

By Richard C. Lewis

In the Dice-K technique, one of the hippocampus’s two memory-shuttling neural pathways (stained green) is blocked. Credit: Toshi Nakashiba, MIT

Susumu Tonegawa has long loved baseball. The Picower Professor of Biology and Neuroscience grew up playing stickball in Japan, and in the more than three decades he has spent in the United States, his love for the game has intensified. So perhaps it shouldn't come as a surprise that Tonegawa's latest scientific innovation honors Daisuke Matsuzaka, the Japanese pitcher who joined the Boston Red Sox last year.

Tonegawa and his colleagues figured out how to manipulate a mouse's genome to produce a toxin that blocks neural transmission in the hippocampus, the central memory-forming area of the brain. Their technique is called doxycycline-inhibited circuit-­exocytosis knockdown, or Dice‑K--a clever nod to Matsuzaka's American nickname. "We want to be playful sometimes," Tonegawa says. "We made a little joke here."

Tonegawa and his team developed Dice‑K in an effort to understand whether the ability to remember new events would be inhibited if a key neural pathway in the hippocampus were blocked. Tonegawa knew that memory formation--whether immediate or occurring through repetition--seemed to involve two such pathways. In a series of experiments with mice, he blocked one of the memory routes, called the trisynaptic pathway, and tested whether the mice would form memories in response to short training regimens.

They didn't, meaning the pathway was crucial to the mice's ability to store and retrieve memories of a recent event. However, when the researchers put the same mice in a maze that they knew well thanks to repeated trials, they had no difficulty recognizing and negotiating their surroundings. This suggested that the other information-carrying route, called the monosynaptic pathway, was sufficient for memory formation through repeated experiences.

"So you can pinpoint where in the brain certain circuits are important for cognition and behavior," says Tonegawa, who won the 1987 Nobel Prize in Physiology or Medicine. "It has opened up a variety of approaches to a variety of questions in neuroscience."

Tonegawa says that since humans have the same memory-forming circuits as mice, his research could lead to ways of improving learning and memory in both healthy people and people with memory disorders such as Alzheimer's and Parkinson's diseases.

Tonegawa doesn't think Matsuzaka knows that his name is linked to science. But he's hoping the pitcher finds out: "We joke in the lab that someone may tell him, and that he'll invite us to Fenway Park."