Oxytocin neurons promote socially-triggered cataplexy

Abstract

Abstract People with narcolepsy often experience intrusive episodes of muscle weakness known as cataplexy which are usually triggered by strong, positive emotions. Importantly, cataplexy almost exclusively occurs during social interactions, so we examined whether the prosocial neuropeptide oxytocin promotes cataplexy and mapped the underlying neural circuits. We show in a murine narcolepsy model that social reunification triggers cataplexy, and that an oxytocin antagonist blocks these socially induced episodes of muscle weakness. Chemo- and optogenetic manipulations reveal that cataplexy is driven by oxytocin receptor-expressing neurons of the central amygdala, which inhibit brainstem neurons that suppress muscle atonia. Remarkably, chocolate, a rewarding stimulus associated with strong, positive emotions also engages this oxytocin-amygdala circuit and triggers cataplexy in narcoleptic mice. This oxytocin pathway helps explain the triggering of cataplexy with social and other rewarding stimuli, and may provide a new opportunity to treat cataplexy.