By Risa Kerslake, RN, BSN

One of the most distressing symptoms of narcolepsy is sudden, involuntary sleep attacks that can hit patients even during activity. Why these sleep attacks occur is a question researchers are still trying to uncover. 

A new study from the University of Toronto has identified a specific subset of brainstem neurons that may be responsible. The findings, published July 8, 2026, in PLOS Biology, identify GABA neurons in the sublaterodorsal tegmental nucleus (SLD) as a previously unrecognized trigger of sleep-attack episodes. 

GABA neurons aid in calming brain activity, but their role in the sleep-wake cycle is less clear. 

Jimmy Fraigne, PhD, an assistant professor in the department of Cell and Systems Biology at the University of Toronto, is aware of the detrimental effects of constant sleepiness in patients with narcolepsy. He set out to answer why people with narcolepsy feel so sleepy that they’re unable to stay awake, even when actively engaged. Understanding the mechanism may lead to a better approach to treatment, he says. 

The researchers worked with both healthy mice and mice bred to lack the chemical orexin, the same chemical missing in human narcolepsy type 1 (NT1). Using optogenetics, a technique that allows researchers to turn specific neurons off and on using light, they tested what happened when these SLD^GABA neurons were turned off. 

“We found that in narcolepsy, when there is a lack of orexin, the brain is out of balance and these neurons become overly active at the wrong time. If we silence them, we can prevent sleep attacks, and conversely, if we activate them even when mice are eating or walking, they will fall asleep in less than a couple of seconds,” explains Fraigne, who led the study. Silencing  SLD^GABA neurons in the orexin-deficient mice also prevented cataplexy, the sudden loss of muscle tone that’s a hallmark symptom of NT1. 

The SLD region is thought to control the rapid eye movement (REM) stage of sleep, but researchers were surprised to discover that activating SLD^GABA neurons primarily promoted non-REM sleep. While GABA cells were thought to be important for controlling the timing of REM sleep, newer studies have suggested it’s actually glutamate cells in the same region that are essential for REM sleep, according to Fraigne. “Our lab found previously that these glutamate cells play an important role in cataplexy. But the GABA cells are really doing the job of putting the ‘brake’ on wakefulness, and when they’re abnormally activated, they can cause sleep attacks in narcolepsy,” he adds.  

While a novel treatment based on the findings is still some time away, Fraigne is encouraged that if the right medication can specifically and exclusively silence SLD^GABA neurons, it could prevent the uncontrollable sleepiness that patients experience.

“Until the discovery of orexin in the late 1990s and the establishment that it is the lack of orexin neurons that causes narcolepsy, we didn’t have a clear understanding of what could help patients,” explains Fraigne. “We show with our study that it is really a question of restoring the balance between wake and sleep tone that might lead to smoother outcomes with fewer side effects.”

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