Neural bases of cataplexy in sleep and emotion control networks – CATAPLExSLEEP

Narcolepsy type 1 is a disabling orphan neurological disorder characterized by excessive daytime sleepiness and cataplexy. Clinical observations have also described an impairment of rapid-eye-movement (REM) sleep regulation with a nighttime premature occurrence of REM sleep episodes and pathognomonic sleep onsets into REM sleep periods. Cataplexy, a specific symptom of narcolepsy, is a loss of skeletal muscle tone triggered, during wakefulness, by positive emotions. The precise pathophysiology involved in spontaneous and emotion-triggered cataplexies is still poorly understood. An influential theory postulates that cataplexy results from an intrusion of REM sleep into wakefulness. In this proposal, we will investigate and manipulate the neural dynamics in the network at the intersection of REM sleep control, muscle atonia and emotional processing in order to better understand cataplexy. To do so, we will combine state of the art multi-units multi-sites recordings and optogenetics with polysomnography and positive/negative emotions behavioral tasks in 2 different rodent models of narcolepsy. The strong and complementary expertise of the 2 academic partners in the domain of sleep, sleep disorders and emotion is a major advantage for the success of the project. This project will significantly contribute to the further understanding of the pathophysiological neural bases of cataplexy. It will provide key insights for future developments of targeted innovative therapeutic approaches and in the long run, for the improvement of the patients’ quality of life