September 23, 2019Neurology
Rapid eye movement, or REM, is one of several sleep stages the body cycles through every night. It first occurs about 90 minutes after falling asleep and is characterized by darting eyes, raised heart rates, paralyzed limbs, awakened brain waves and dreaming. For more than a century, scientists have explored the role of sleep in storing memories. While many have shown that sleep helps the brain store new memories, others, including Francis Crick, the co-discoverer of the DNA double helix, have raised the possibility that sleep - in particular REM sleep - may be a time when the brain actively eliminates or forgets excess information. Moreover, recent studies in mice have shown that during sleep - including REM sleep - the brain selectively prunes synaptic connections made between neurons involved in certain types of learning. However, until this study was published, no one had shown how this might happen.
REM sleep is a fascinating period when most of our dreams are made. Now, in a study of mice, it has been shown that it may also be a time when the brain actively forgets. The study results, published in Science (19 September 2019), suggest that forgetting during sleep may be controlled by neurons found deep inside the brain that were previously known for making an appetite stimulating hormone. The authors, have spent years examining the role of a hormone called hypocretin/orexin in controlling sleep and narcolepsy. Narcolepsy is a disorder that makes people feel excessively sleepy during the day and sometimes experience changes reminiscent of REM sleep, like loss of muscle tone in the limbs and hallucinations. The authors and others have helped to show how narcolepsy may be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus, a peanut-sized area found deep inside the brain. For the study, the authors looked at neighboring cells that produce melanin concentrating hormone (MCH), a molecule known to be involved in the control of both sleep and appetite. In agreement with previous studies, the authors found that a majority (52.8%) of hypothalamic MCH cells fired when mice underwent REM sleep whereas about 35% fired only when the mice were awake and about 12% fired at both times. The authors also uncovered clues suggesting that these cells may play a role in learning and memory. Electrical recordings and tracing experiments showed that many of the hypothalamic MCH cells sent inhibitory messages, via long stringy axons, to the hippocampus, the brain's memory center.
To test this idea, the authors used a variety of genetic tools to turn on and off MCH neurons in mice during memory tests. Specifically, the authors examined the role that MCH cells played in retention, the period after learning something new but before the new knowledge is stored, or consolidated, into long term memory. The authors used several memory tests including one that assessed the ability of mice to distinguish between new and familiar objects. Unexpectedly, it was found found that turning on MCH cells during retention worsened memory whereas turning the cells off improved memories. For instance, activating the cells reduced the time mice spent sniffing around new objects compared to familiar ones, but turning the cells off had the opposite effect. Further experiments suggested that MCH neurons exclusively played this role during REM sleep. Mice performed better on memory tests when MCH neurons were turned off during REM sleep. In contrast, turning off the neurons while the mice were awake or in other sleep states had no effect on memory.
According to the authors, the results suggest that MCH neurons help the brain actively forget new, possibly, unimportant information. The authors added that since dreams are thought to primarily occur during REM sleep, the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus - consequently, the dream is quickly forgotten.
In the future, the authors plan to explore whether this new circuit plays a role in sleep and memory disorders.