Oxytocin promotes socially triggered cataplexy by activating central amygdala neurons in narcoleptic mice

Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy, sudden episodes of muscle weakness triggered by strong emotions like laughter or anger. These debilitating attacks almost exclusively occur during social interactions, yet the precise neural mechanisms linking social cues and emotional processing to cataplexy remain poorly understood. Current treatments often manage symptoms but don't fully address the underlying triggers. This study investigates the role of oxytocin, a neuropeptide known for its prosocial effects, in mediating socially-triggered cataplexy.

Researchers utilized a mouse model of narcolepsy to investigate the role of oxytocin in cataplexy. The primary experimental setup involved inducing cataplexy through social reunification. To assess oxytocin's involvement, an oxytocin antagonist was administered to block its effects. The study also employed chemo- and optogenetic manipulations to precisely control the activity of oxytocin receptor-expressing neurons within the central amygdala. Activity of these neurons and oxytocin tone were monitored just before cataplexy episodes. The primary endpoint was the occurrence and frequency of cataplexy episodes.

This study revealed that social reunification reliably triggered cataplexy in narcoleptic mice. Crucially, administration of an oxytocin antagonist effectively blocked these socially induced cataplexy episodes. > Oxytocin tone and the activity of oxytocin receptor-expressing neurons in the central amygdala both significantly increased just prior to cataplexy triggered by social stimuli. Further chemo- and optogenetic manipulations demonstrated that oxytocin-responsive neurons in the central amygdala actively drive cataplexy. This occurs by inhibiting specific brainstem neurons responsible for suppressing muscle atonia, thereby allowing the sudden muscle weakness characteristic of cataplexy. Interestingly, a rewarding stimulus like chocolate, also associated with strong positive emotions, was found to engage this same oxytocin-amygdala pathway, similarly triggering cataplexy in the narcoleptic mouse model.