Sleep disorders

Studying sleep disorders is of great interest to get a better understanding of their etiology and physiopathology, to provide new data helping for the development of innovative treatments but also to study the physiology of natural sleep.

We are currently focusing on two main sleep pathologies: narcolepsy type 1 and REM sleep behavior disorder (RBD).

Narcolepsy type 1 is a chronic and rare neurology disorder of sleep, characterized by excessive daytime sleepiness accompanied with irresistible sleep attacks, disrupted nighttime sleep, hypnagogic hallucinations, sleep paralysis and cataplexy. Specific features of narcolepsy are abnormal sleep onset into REM sleep and sleep fragmentation indicating dysregulation of REM sleep and unconsolidated sleep and wake states. Cataplexy is a major pathognomonic symptom of narcolepsy, described as a loss of muscle tone during active wake, triggered by positive emotion while consciousness is preserved. NT1 is the consequence of the loss of hypocretin/orexin neurons, likely of autoimmune origin.

REM sleep behavior disorder (RBD) is the best prodromal marker at 10 years of α-synucleinopathies including Parkinson's Disease (PD). In RBD, REM sleep is marked by the irreversible loss of muscle atonia, thus facilitating the occurrence of abnormal, uncontrolled and inconscious motor activities suggesting that RBD patients enact their dreams  and inner oniric activities during REM sleep. Our hypothesis (hypertext links to Valencia Garcia et al, 2018b, c) currently under investigation is that RBD may be due to an α-synuclein-dependent attack targeting neurons that generate muscle atonia during REM sleep we recently circumscribed in rodents (hypertext link to Valencia Garcia et al, 2017, 2018a).

Our projects are translational using multidisciplinary approaches and cutting edge technologies (single cell transcriptomic; shRNA inactivation; opto-chemogenetics; crispr-cas9; multi-units multi-sites recordings) aiming at studying :

• Mechanisms of neuroinflammation leading to the death of orexin/hypocretin neurons and thus of narcolepsy type 1;
• Characterization of cataplexy in mice and human NT1;
• Identification of the neuronal circuits of cataplexy ;
• α-synuclein-dependent mechanisms responsibles for RBD and its pheno-conversion into Parkinson’s Disease ;
• Origin of the abnormal motor activities occuring during REM sleep in rodent models : an opened window to dreams ?
• Development of rodent models of sleep pathologies ;
• Preclinical studies for innovative treatments.