U of T neurobiologists discover switch that turns muscles on and off – News@UofT

In aYouTube videowith nearly 12 million views, a young woman stands facing the camera, giving a dance lesson. Mid-sentence, her legs buckle and she collapses to the floor. She sits upright groggily butseconds later, her upper body and head slump forward and she lies motionless. After a few seconds, she sits upright, eyes open, but struggles to remain vertical. She slumps back against the wall, shakes her head and tries unsuccessfully to stand.

As explained in the captions that accompany the video, the woman suffers from narcolepsy with cataplexy. Narcolepsy is a sleeping disorder characterized by excessive sleepiness or the uncontrolled onset of sleep; its often accompanied by cataplexy, a complete loss of muscle control or muscle tone. Its cataplexy that caused the womans legs to give out from under her even though she was awake; it was narcolepsy that put her to sleep seconds later.

Unless you suffer from cataplexy, you probably arent aware of how the muscle tone present in your body affects you. A moderate amount of muscle tone is normal and necessary. As the video illustrates, it keeps us from falling when were standing, keeps us upright when we sit and is even keeping your head vertical as you read this.

There are also times when a complete lack of muscle tone is normal and necessary. During rapid eye movement (REM) sleep, its absence paralyzes us, thereby preventing us from flailing our arms and legs as we dream were swimming or riding a bicycle.

John Peever,a neurobiologist in thedepartment of cell and systems biology(CSB) in the Faculty of Arts & Science, studies how the intricate circuitry of the brain orchestrates muscle tone with our state of arousal to ensure our muscles are doing what theyre supposed to be doing when were asleep and awake.

Peever and a team of collaborators recently conducted an experiment demonstrating that the area of the brain called the sublaterodorsal tegmental nucleus, or SLD already known to induce muscle paralysis during REM sleep can also trigger cataplexy.

We manipulated the SLD in the brains of mice which allowed us to turn this circuit on or off, says Peever. The researchers showed that when the SLD was deactivated, mice moved normally. When the SLD was activated, the mice became cataplectic meaning they became completely immobile even though they were awake.

Our experiment was the first clear demonstration that this area of the brain causes cataplexy, says Peever. It showed that the SLD has the capacity to decouple brain state and muscle tone during wakefulness.

It was remarkable to see how altering the activity of such a tiny brain area changed the normal behavior of healthy mice, says Peever. After watching these experiments, we realized that we had opened a window into how the brain functions in cataplexy. Its one thing to have an idea about how the brain functions, but its an entirely different thing to see it live in action.

Peever and his collaborators, including CSB research associateJimmy Fraigneand colleagues from U of Ts departments of physiology and medicine in the Faculty of Medicine, published the results of their experiment in the journalCurrent Biologylast fall.

Peever hopesthe research could lead to treatments for patients experiencing a variety of muscular disorders. For example, patients with cerebral palsy can experience uncontrollable shaking; babies with a genetic disorder called hyperexplexia become paralyzed when they hear a loud, sudden noise.

As well, the muscles of Parkinsons patients are in a continual state of rigour, making everyday activities like climbing stairs or getting into bed virtually impossible.

Its as if their muscle tone is in a constant state of overdrive with one exception. When a Parkinsons patient experiences REM sleep, their muscle tone is turned off as it is in a person without the disease.

When a Parkinsons patient enters REM sleep their whole body relaxes and their movements become perfectly normal, says Peever.

Now that weve found that this circuit in the brain switches muscle tone on and off, that makes us think: Wouldnt it be wonderful if we could come up with a volume control for the SLD in Parkinson's patients that allowed us to set muscle tone at just the right level? At least, thats my dream.

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U of T neurobiologists discover switch that turns muscles on and off - News@UofT