茄子直播

茄子直播 neurobiologists discover switch that turns muscles on and off

John Peever and Jimmy Fraigne
John Peever, a neurobiologist in the department of cell and systems biology, and research associate Jimmy Fraigne hope their research could lead to treatments for a variety of muscular disorders (photo by Diana Tyszko)

In a  with 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 but seconds 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; it鈥檚 often accompanied by cataplexy, a complete loss of muscle control or muscle tone. It鈥檚 cataplexy that caused the woman鈥檚 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 aren鈥檛 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 we鈥檙e 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 we鈥檙e swimming or riding a bicycle.

John Peever, a neurobiologist in the department 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 they鈥檙e supposed to be doing when we鈥檙e 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 鈥 already known to induce muscle paralysis during REM sleep 鈥 can also trigger cataplexy.

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

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

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

Peever and his collaborators, including CSB research associate Jimmy Fraigne and colleagues from 茄子直播鈥檚 departments of physiology and medicine in the Faculty of Medicine, published the results of their experiment in the journal  last fall.

Peever hopes the 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 Parkinson鈥檚 patients are in a continual state of rigour, making everyday activities like climbing stairs or getting into bed virtually impossible. 

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

鈥淲hen a Parkinson鈥檚 patient enters REM sleep their whole body relaxes and their movements become perfectly normal,鈥 says Peever.

鈥淣ow that we鈥檝e found that this circuit in the brain switches muscle tone on and off, that makes us think: Wouldn鈥檛 it be wonderful if we could come up with a 鈥榲olume control鈥 for the SLD in Parkinson's patients that allowed us to set muscle tone at just the right level? At least, that鈥檚 my dream.鈥

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