RU researchers find that waking experiences influence the brain's gene expression during REM sleep

Mammals spend a large portion of their lives sleeping. In addition to allowing the body to rest, sleep seems to play a role in the consolidation of daytime memories. A number of scientific observations have supported the idea that the brain is reactivated during sleep to process sensorimotor information, but how the brain did this remained unknown. In a recent paper in Learning & Memory, a team of Rockefeller scientists show that the expression of a gene linked to the modification of neuronal connections went up during the deepest phase of sleep that follows an enriched waking experience. The team suggests that this could provide a mechanism by which sleep contributes to the consolidation of memories of daytime events.

Most mammals have two distinct phases of sleep: slow wave (SW) and rapid eye movement (REM), the deepest phase of sleep. In humans, dreaming occurs during REM sleep. “We can’t really assess dreaming in animals,” says Sidarta Ribeiro, first author on the paper, “but we can assess REM sleep.” Ribeiro worked with Assistant Professors Claudio Mello and Constantine Pavlides and Science Outreach student Vikas Goyal to monitor gene activation in the rat brain during the different phases of wakefulness and sleep.

The researchers focused their efforts on the gene zif-268 because its expression in the brain is known to be highly sensitive to neuronal depolarization (Ribeiro and Mello were concurrently studying expression of the ZENK gene in canaries, which is the homolog of zif-268). They reasoned that if they measured this gene expression in rats, they would see an increase in neural activity during REM sleep. But their early results didn¹t confirm the hypothesis. Instead, the gene expression went down, not up, during REM sleep.

This was puzzling, until they decided to look at the problem another way. Ribeiro notes that some European scientists had suggested to approach the cognitive function of sleep the way one would approach the digestive system: what¹s going on inside depends on how much the system is being fed. The rats in the RU experiments had intentionally been held and calmed to factor out stress as a reason for gene expression. Perhaps their gene expression went down during sleep because the rats didn¹t have a stimulating enough waking experience to warrant more extensive neuronal activity. To reexamine the REM question, the scientists decided to “feed the system.”

They devised a rat’s idea of a fun house: a labyrinth with various forms of sensory stimulation that included tunnels, platforms, wooden toys, and five different flavors of scented corn flakes, so as to stimulate exploratory behavior. A group of rats was put in this environment three hours before the sleep experiments (this kind of exposure is known to elicit a rapid and transient induction of zif-268). Later, when the animals entered REM sleep, zif-268 expression was upregulated, just as the researchers had hoped it would. In contrast, the control group of animals (who did not experience the stimulating maze) showed no gene reactivation during REM sleep. Thus the activity of the brain and its gene expression patterns during REM sleep seems to be influenced by what the animal has experienced while awake.

Ribeiro and his co-authors believe that this gene reactivation indicates a window of increased neuronal plasticity, during which the brain might be making new connections. The formation and modification of synaptic connections, based on several lines of evidence, seems at the very heart of the formation of long-lasting memories. Hence, it is conceivable that this window of increased plasticity during REM sleep represents a mechanism for the role of sleep in the consolidation of memories.

This study differs from other rat sleep experiments because the animals were allowed normal sleep patterns. Other labs have looked at the difference between rats that are sleep deprived and rats that sleep normally. Mello points out that his and Ribeiro¹s background in the Animal Behavior lab at RU gave them a different perspective.

“What happens to animals who are deprived of sleep is not necessarily a good indicator of what sleep does,” says Mello. “We learned from our experiments with birds that it¹s important to look at the natural behaviors.”