By listening in on the chatter between neurons in various parts of the brain, researchers from the California Institute of Technology (Caltech) have taken steps toward fully understanding just how memories are formed, transferred, and ultimately stored in the brain--and how that process varies throughout the various stages of sleep.

Their findings may someday even help scientists understand why dreams are so difficult to remember.

Scientists have long known that memories are formed in the brain's hippocampus, but are stored elsewhere--most likely in the neocortex, the outer layer of the brain. Transferring memories from one part of the brain to the other requires changing the strength of the connections between neurons and is thought to depend on the precise timing of the firing of brain cells.

"We know that if neuron A in the hippocampus fires consistently right before neuron B in the neocortex, and if there is a connection from A to B, then that connection will be strengthened," explains Casimir Wierzynski, a Caltech graduate student in computation and neural systems, and first author on the Neuron paper. "And so we wanted to understand the timing relationships between neurons in the hippocampus and the prefrontal cortex, which is the front portion of the neocortex."

The research team--led by Athanassios Siapas, a Bren Scholar in the Caltech Division of Biology and an associate professor of computation and neural systems--used high-tech recording and computational techniques to listen in on the firing of neurons in the brains of rats. These techniques helped them pinpoint a number of neuron pairs that had precisely the kind of synchronous relationship they were looking for--one in which a hippocampal neuron's firing was followed within milliseconds by the firing of a neuron in the prefrontal cortex.

"This is exactly the kind of relationship that would be needed for the hippocampus to effect changes in the neocortex--such as the consolidation, or laying down, of memories," adds Wierzynski.

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Once these spike-timing relationships between the hippocampal and prefrontal cortex neurons had been established, the team used their high-tech eavesdropping techniques to hear what goes on in the brains of sleeping rats--since sleep, as Siapas points out, has long been thought to be the optimal time for the memory consolidation.

As it turns out, those thoughts were right--but only part of the time.

The team did indeed hear "bursts" of neuronal chatter during sleep--but only during a phase of sleep known as slow-wave sleep (SWS), the deep, dreamless periods of sleep. "It turns out that during slow-wave sleep there are these episodes where a lot of the cells in the hippocampus will all fire very close to the same time," says Wierzynski. In response, some cells in the prefrontal cortex will fire in near unison as well, just milliseconds later. "What's interesting is that the bulk of the precise spike timing happens during these bursts, and not outside of these bursts," he adds.

On the other hand, during rapid-eye-movement (REM) sleep, the previously chatty neuron pairs seemed to talk right past each other, firing at the same rates as before but no longer in concert.

"It was surprising," says Wierzynski, "to find that the timing relationship almost completely went away during REM sleep."

Since REM sleep is the phase during which dreaming occurs, the scientists speculate that this absence of memory-consolidating chatter may eventually help to explain why dreams can be so difficult to remember.

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As intriguing as that idea may be, the researchers caution that these findings only raise possibilities, providing avenues for further research in the field.

"Now that we've shown this link," says Siapas, "we have a framework we can use to study these questions further. This is just a step toward our goal of some day fully understanding the relationship between memory and sleep."

Other coauthors on the paper included Evgueniy Lubenov, a postdoctoral scholar in biology at Caltech, and Caltech graduate student Ming Gu.

This work was supported by a National Defense Science and Engineering Graduate Fellowship, the Caltech Information Science and Technology Center for Biological Circuits Design, the James S. McDonnell Foundation, the Bren Foundation, the McKnight Foundation, the Whitehall Foundation, and the National Institutes of Health.