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New University of Toronto research shows that two powerful brain chemical systems work together to paralyze skeletal muscles during rapid eye movement (REM) sleep.

The findings, published in the July 18 issue of The Journal of Neuroscience, may help scientists better understand the causes of sleep disorders such as narcolepsy, tooth grinding, and REM sleep behaviour disorder.

“The study’s findings are relevant to anyone who has ever watched a sleeping pet twitch, gotten kicked by a bed partner, or has known someone with the sleep disorder narcolepsy,” said Dennis J. McGinty, PhD, a behavioral neuroscientist and sleep researcher at the University of California, Los Angeles, who was not involved in the study.

The research could be especially helpful for those with REM sleep disorder, a disease that causes people to act out their dreams.

“Understanding the precise mechanism behind these chemicals’ role in REM sleep disorder is particularly important because about 80 percent of people who have it eventually develop a neurodegenerative disease, such as Parkinson’s disease,” said study author John Peever, PhD, a U of T neuroscientist.

“REM sleep behaviour disorder could be an early marker of these diseases, and curing it may help prevent or even stop their development,” Peever added.

During REM sleep — the deep sleep where most recalled dreams occur — your eyes continue to move but the rest of the body’s muscles are stopped, potentially to prevent injury, by specialized cells in the brain called motor neurons.

In a series of experiments measuring the electrical activity in the facial muscles of sleeping rats, Peever and U of T neuroscientist Patricia Brooks used a neurotransmitter known as GABA (for gamma-aminobutyric acid) and another neurotransmitter called glycine to switch off the motor neurons in rats. The result: REM sleep paralysis.

This finding reversed earlier beliefs that only glycine inhibited these motor neurons.

"We showed that GABA and glycine shut off motor neurons during REM sleep and that's what triggers REM paralysis," said Peever. "But we also identified the way cells detect GABA and glycine.

"Motor neurons, like all brain cells, listen to these transmitters through receptors and we identified the receptors that allow GABA and glycine to shut the motor neurons off - the three different types of receptors that are required."

Previous research had suggested that only the neurotransmitter receptors for glycine caused sleep paralysis. However, when the researchers blocked these receptors, sleep paralysis still occurred.

To prevent REM sleep paralysis, the researchers found they also had to block receptors for GABA. Only once the motor cells were cut off from all sources of both GABA and glycine did the paralysis fail to occur. The data suggest the two neurotransmitters must both be present together to maintain motor control during sleep, rather than working separately.

“By identifying the neurotransmitters and receptors involved in sleep-related paralysis, this study points us to possible molecular targets for developing treatments for sleep-related motor disorders, which can often be debilitating,” McGinty said.

This study was funded by the Canadian Institutes of Health Research and the National Science and Engineering Research Council of Canada.