CATAPLEXY TRIGGERED BY SOCIAL CUES: A ROLE FOR OXYTOCIN IN THE AMYGDALA

Abstract Introduction People with narcolepsy type 1 report that cataplexy is triggered most often by positive social experiences such as laughing with friends, yet the mechanisms through which social interaction promotes cataplexy are unknown. We hypothesize a subpopulation of central amygdala neurons that are sensitive to the prosocial neuropeptide, oxytocin (CeAOTR), respond to positive valence and trigger cataplexy. Methods We have used in vivo calcium imaging, chemogenetic and optogenetic approaches to characterize the activity pattern of these neurons and to manipulate their activity state. Results Cre-dependent anterograde tracing of the CeAOTR neurons of the central amygdala indicate a moderate to dense projection to the REM sleep-regulatory region of the ventral lateral periaqueductal gray (vlPAG). Additionally, Channel Rhodopsin Assisted Circuit Mapping (CRACM) experiments show that CeAOTR neurons inhibit vlPAG neurons that innervate the REM atonia-promoting region, the sublaterodorsal nucleus. Targeted photostimulation (15Hz (10ms) for 20sec every hour) of the CeAOTR fibers in the vlPAG doubled the amount of cataplexy. Preliminary in vivo calcium imaging indicates that the CeAOTR are active just prior to the onset of cataplexy. Chemogenetic and optogenetic activation of CeAOTR neurons increased cataplexy. Conclusion We conclude that the CeAOTR subpopulation is sufficient to promote cataplexy. Our future directions include determining the necessity of these oxytocin sensitive neurons in cataplexy under different conditions of positive valence. Support R01 NS106032 and WakeUp Narcolepsy.