A New Clue to Why Laughter Can Trigger Cataplexy

By FitNews On Jul 29, 2026

By Alyx Arnett

For people with narcolepsy type 1, cataplexy most often strikes during life’s happiest moments—laughing with family, playing games, or unexpectedly running into a friend.¹ Despite this well-known pattern, researchers have never fully understood why positive social experiences can suddenly trigger the loss of muscle tone.

A new study points to oxytocin—the hormone best known for its role in social bonding—as a key part of the answer.² Because positive social interactions are known to increase oxytocin release, researchers investigated whether the neuropeptide helps explain why those same moments can trigger cataplexy.

In a mouse model of narcolepsy, they found that oxytocin activates a brain pathway that appears to drive cataplexy during positive social interactions.

“We had a feeling it was either oxytocin or some other social-related hormone [that] was going to increase cataplexy,” says Carrie Mahoney, PhD, an instructor in neurology in the Division of Sleep Medicine at Harvard Medical School and the study’s corresponding author. “But we weren’t sure.”

Isolating the Oxytocin Circuit

Mahoney says the team focused on oxytocin because years of research had already established its role in social behavior. Previous studies had also identified oxytocin-sensitive neurons in the amygdala, a brain region already implicated in regulating muscle tone.

The first step was determining whether social interaction actually increased cataplexy in the mouse model. The team developed a social isolation and reunification test, briefly separating mice from their littermates before bringing them back together.

When the mice were reunited, cataplexy increased compared with the baseline period. Control experiments ruled out other explanations, including novelty, general arousal, and the stress of repeated handling, showing that social interaction itself was driving the increase in cataplexy.

Next, the team tested whether oxytocin was actually responsible by using an oxytocin receptor antagonist to block oxytocin signaling. Indeed, this averted the socially-triggered cataplexy during the reunification tests.“By blocking oxytocin, we could prevent the increase in cataplexy,” Mahoney says.

The team then tested the opposite approach, giving the mice an oxytocin receptor agonist (carbetocin). Administering the agonist increased both the amount of time the mice spent in cataplexy and the number of cataplexy bouts compared to a saline control.

Mapping the Neuronal Pathway

Finding that oxytocin was involved still left a major question: Where in the brain was it acting? The team focused on oxytocin-producing neurons that project from the brain’s paraventricular nucleus to the central amygdala, a region already linked to cataplexy. Stimulating those nerve endings increased cataplexy in the mice.

The researchers also wanted to know whether oxytocin signaling in the central amygdala naturally increases before a cataplexy episode. They implanted an oxytocin sensor into the central amygdala and recorded the activity using fiber photometry. The oxytocin signal typically increased just before the onset of socially-elicited cataplexy. In 20 out of 34 recorded bouts, social contact occurred within 24 seconds before the onset of the episode.

Rather than discovering an entirely new pathway, Mahoney says the team’s contribution to cataplexy-circuit knowledge is in identifying the specific oxytocin-sensitive neurons within a broader circuit that had already been linked to cataplexy.

“We drilled even further down to a subpopulation, trying to understand the oxytocin-sensitive neurons within that broader inhibitory population,” Mahoney says. “We are contributing the specificity of oxytocin-sensitive neurons to the pathway.”

The team’s circuit mapping showed that these oxytocin-sensitive neurons shut down brainstem neurons that normally suppress muscle atonia. In effect, turning off that protective pathway allows cataplexy to occur.

Overlapping Reward Circuitry

The researchers next wanted to know whether the newly identified circuit responded only to social interaction—or to rewarding experiences more broadly. To find out, they gave the mice milk chocolate.

The chocolate recruited the same oxytocin-amygdala pathway and triggered cataplexy. “Rewarding stimuli or motivating stimuli taps into similar or the same neuronal circuitry,” Mahoney says.

The team also wanted to know whether activating those neurons was rewarding to the mice. Using a real-time place preference test, they found the mice consistently preferred the chamber where those neurons were stimulated.

Mahoney says the findings don’t necessarily mean chocolate and social interaction activate identical populations of neurons. There could be other, as-yet-unidentified neurons involved. However, the results suggest both types of rewarding experiences recruit similar oxytocin-sensitive pathways.

“As the social interaction is positive, and whether it’s a treat or some other rewarding stimulus, they’ll more likely be recruiting similar pathways,” Mahoney says.

Although food isn’t a common trigger for people with narcolepsy type 1, Mahoney notes that in more severe cases, highly rewarding experiences—including food—can occasionally bring on cataplexy.

Therapeutic Implications

The findings also raise an important question: Could this pathway become a treatment target?

Although blocking oxytocin signaling reduced cataplexy in the mouse model, Mahoney says she wouldn’t want to block oxytocin itself in people. Because the neuropeptide plays such an important role in emotional processing and social bonding, doing so could create unwanted side effects.

“You don’t want to interrupt normal human behavior or normal social interactions with any of this targeted treatment,” Mahoney says. “You could potentially limit the benefits of social interaction, which we would not want to do at all.”

Instead, Mahoney says the goal is to better understand the oxytocin-sensitive neurons themselves. By identifying the biological markers of those cells, researchers hope to identify other features of those neurons that could eventually serve as therapeutic targets.

“Maybe there’s an alternative target other than the oxytocin receptor,” Mahoney says. “Maybe there’s something else in there that we could target that would allow for normal behavior but suppress the cataplexy.”

Translating these findings to people will be much harder. Mahoney says researchers can’t directly observe these same neural circuits in living people. For now, they are largely limited to imaging techniques, such as functional MRI, to determine whether the same brain regions become active during cataplexy.

Mahoney says her next step is securing funding to continue studying these oxytocin-sensitive neurons in hopes of identifying those alternative therapeutic targets.

Unexpected Variances in Juvenile Females

One finding surprised Mahoney. During the behavioral testing, juvenile female mice experienced substantially more cataplexy than any other group, including both adult mice and juvenile males—roughly twice as many episodes as the other groups, and their responses were considerably more variable, by Mahoney’s estimation.

Although the study wasn’t designed to investigate sex differences, Mahoney says the finding raises questions about whether developmental changes could influence cataplexy susceptibility.

“Maybe it’s just the juvenile nature,” Mahoney says. “Maybe something’s developing in the brain, which leaves the females more likely to have more cataplexy.”

She notes that relatively little research has explored whether symptom severity differs by sex in people with narcolepsy, suggesting the observation could warrant further study.

Validating the Patient Experience

For Mahoney, one of the study’s most important contributions is providing a biological explanation for something people with narcolepsy have described for years: why positive social interactions can trigger cataplexy.

Rather than simply describing the pattern, she says the findings identify a physical brain circuit that helps explain how rewarding social experiences can lead to muscle atonia.

“It’s a physical circuit, which is difficult for patients to be able to address in the moment,” Mahoney says.

That, she says, underscores an important message for patients and clinicians alike.

“Their symptoms are valid, and we need to help them be able to live as normal a life as possible by helping them develop therapies to address it,” Mahoney says.

References

Overeem S, van Nues SJ, van der Zande WL, et al. The clinical features of cataplexy: a questionnaire study in narcolepsy patients with and without hypocretin-1 deficiency. Sleep Med. 2011;12(1):12-8.
Mahoney CE, De Luca R, Joyal AA, et al. Oxytocin promotes socially triggered cataplexy. Nat Neurosci. Published online 2026, July 14.

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