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Matthew Wilson
Picower Institute researcher, biology and BCS faculty member

What is sleep’s role in memory formation?

Enter the BCS complex from Vassar Street, and you’ll be greeted by the Picower Institute’s mission statement, chiseled into the white stone wall along the central stairway. Venture up the stairway to Matthew Wilson’s airy, high-ceilinged office and labs, and you’ll see that mission in action. In the device fabrication lab he helped design, Wilson picks up what looks like a very fine silver hair – four delicate electrodes twisted together. He uses groups of these wires to probe into the brains of rats and mice in order to study the role of sleep in memory formation and maintenance.

Neurons communicate by means of electrical signaling, which Wilson’s electrodes monitor. “It’s like we’re listening in on a conversation in a room full of people by lowering a microphone into the room,” he says. Like a microphone, the twist of wires can be moved, “so that when it gets close to the cells we can listen for activity.” Wilson, who has an electrical-engineering background, “listens” to the electrical activity of 50 to 100 cells at a time with an array of about 20 electrodes.

Wilson eavesdrops on neurons in the hippocampus, a structure deep in the mammalian brain that plays an important role in the formation and upkeep of memories, and in part of the neocortex, the area of the brain responsible for activities ranging from motor coördination to conscious thought in humans. His research appears to support the theory that during sleep, memories are edited and transferred from short- to long-term storage.

When rats and mice walk down a familiar path, Wilson has found, groups of neurons in their hippocampi are activated in a particular sequence. In his labs, rats and mice traverse mazes wearing strange crowns of circular electrode arrays. The electrodes reach the rodents’ brains through holes drilled into their skulls; screws on the arrays let Wilson move the electrodes up or down. Long wires connect the arrays to computers that collect data about neural activity, while overhead cameras track the animals’ positions in the mazes. “We can tell where the animal is in the maze just by looking at activity patterns in the hippocampus,” says Wilson. “As the animal moves, the patterns change. It’s sort of like a movie of the animal’s experience.”

Once they know what this “movie” of signaling patterns looks like, Wilson and his colleagues can watch for a rerun while the mouse is sleeping or sitting quietly. They also look for repeats of the pattern in the neocortex. Using his electrodes, Wilson can monitor the “whole process of experiencing the world and turning it into patterns of activity in the brain.” He then looks for changes in activity patterns that suggest the rodents are forming and editing memories. Wilson is also working with Picower Institute director Susumu Tonegawa to identify the genetic basis of the signaling patterns.

Wilson and his lab mates believe that they have identified memory-related activity in almost all stages of sleep. During light sleep, Wilson says, the rodents play back “brief snippets that are much faster than they were experienced – rapid, MTV-like flashes.” He thinks this means the animals are dreaming about recent experiences. In contrast, “during REM [rapid eye movement] sleep, memory seems to be played out in real time,” which he says suggests “revisiting old experiences, comparing things, and trying to synthesize.” Wilson likens the neural activity during light sleep to preliminary sorting through a pile of papers to decide what’s important and what can be trashed, the in-depth playback of REM to “when you put together the information you have into something more usable.” He has also found that when the mice and rats are doing things that don’t require active attention – such as eating – they go into a sleeplike state and “play back what they were just doing.”

Wilson suspects that if he could monitor human brains with electrodes, he would see similar phenomena. “Mice and human brains differ, but the overall structures in the brains are very similar,” he says. “There’s every indication that there’s something similar in humans.” – By Katherine Bourzac, SM ‘04

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