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Ramped up information processing in the hippocampus during sleep suggests to Jeff Magee that the brain uses this "downtime" to replay the day's events.
Furthermore, the computer can tease out other details from the data, identifying previously undetected features in the electrical activity underlying sleep's stages. "Some of the work we're doing in my lab has actually overturned a lot of the beliefs in the textbooks about the different sleep states," Sejnowski says.
For one thing, Low's and Sejnowski's computer analysis shows that the rapid eye movement (or REM) sleep associated with dreaming does not, in fact, show basically the same electrical activity as an awake brain, as textbooks assert.
Besides REM, sleepers cycle through several other phases, including an intermediate state of sleep (with a mix of slow and fast electrical activity) and deeper, "slow-wave" sleep. Some studies have identified slow-wave sleep as important for firming up memories, but work from Sejnowski's lab suggests that intermediate sleep may play a more significant role in memory formation. His analyses have detected new patterns of activity within that state.
At times during intermediate sleep, the research indicates, cortex electrical activity rapidly alternates between high frequencies and low frequencies every few seconds. "We think that's going to be the best place to look for the biochemical changes that are occurring [during sleep]. In some cases you can spend half your sleeping hours in intermediate sleep," says Sejnowski, "and I think that's where the key to understanding the true function of sleep is going to be found."
Intermediate sleep is marked by brief bursts, or "spindles," of electrical signaling produced by the thalamus, an important relay station for transmitting information between the cortex and various other parts of the brain. Those spindles recur every few seconds, setting up synchronized electrical oscillations throughout the cortex. Sejnowski hypothesizes that the spindle activity puts the brain into a state conducive to storing new memories without interference from other activity.
New details about sleep's role in memory also come from HHMI's Janelia Farm Research Campus in Ashburn, Virginia, where Jeffrey C. Magee and his team seek help from rats to decipher sleep's mysterious methods. Magee and collaborators perform experiments impossible in live animals by extracting slices of living neurons from a rat brain and recording their electrical activity.
Memory storage is believed to involve the strengthening of synapses, the junctions connecting neurons. To build stronger synapses, the neuron must be studded with abundant quantities of protein molecules that sense the neural messenger molecule glutamate. When deprived of sleep, the neurons display fewer of those sensor proteins, and the ability to make permanent memories diminishes, Magee's research shows.
"If you don't get enough sleep, you mess up this whole process of keeping the right amounts of membrane proteins at their right locations inside the cell," he says.
Magee and his colleagues study slices of rat neurons taken from the hippocampus, the brain region that plays a prominent role in forming long-term memories. Those neurons retain their connections and signaling patterns, responding to the stimulus of messenger molecules just as neurons in a living animal do. Magee and colleagues have developed techniques to deliver those messenger chemicals to specific neurons, thereby stimulating the slices into states similar to those found in either the awake or sleeping animal. In the "awake" neurons, input from other cells flows in haphazardly, and a neuron fires its electrical signals based on the summed-up influences of all those inputs.
"In the sleep state, we see a very different kind of output pattern," says Magee, who reported on his work in the February 2006 issue of The Journal of Neuroscience. The same information is processed, but much more rapidly and precisely. The signaling speed is accelerated to 20 times the original rate. So it seems that during sleep, the cells from the hippocampus may be replaying the day's activity.
"In fact, the networks that are involved in the replay are the exact same sets of cells that actually process that information to begin with," he says.
Photo: Tim Mantoani
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