En francais :

Le cerveau humain, ainsi que celui de tous les vertébrés supérieurs, est soumis à l'alternance cyclique de l'éveil et du sommeil. L'objectif majeur des recherches menées dans notre laboratoire (INSERM-U52/CNRS-URA1195, Département de Médecine Expérimentale à l’Université Claude Bernard, 1957-1998, fondés et dirigés par le Pr. Michel Jouvet et INSERM-U480, 1998-2002, sous la responsabilité du Dr. Raymond Cespuglio) a été d'élucider les mécanismes neurobiologiques responsables du sommeil, en particulier du sommeil paradoxal et de comprendre les fonctions du sommeil et du rêve. Depuis le 1er janvier 2004, notre nouvelle unité (INSERM-U628) intitulée « Physiologie intégrée du système d’éveil » est créée au sein du Département de Médecine Expérimentale et notre projet consiste à démontrer les mécanismes centraux responsables du maintien de l’éveil et de la vigilance et nos études sont focalisées sur les neurones à histamine et à orexine.

Mots clefs : éveil, sommeil, sommeil lent, sommeil paradoxal, activation corticale, hypothalamus postérieur, histamine, orexin, tegmentum mésopontique, substance éveillante, somnolence, trouble de vigilance, neurophysiologie, chat, souris

In english :

Our goal is to unravel the mechanisms of wake and associated pathologies: narcolepsy, excessive daytime sleepiness, insomnia, metabolic disorders, sudden infant death syndrome.

From a basic research standpoint, we dissect the mechanisms of wake through the study of the specific, complementary and synergistic roles of histaminergic and orexinergic neurons in particular. Using specific knock out mice and detailed behavioral and electroencephalographic measures, we will determine how the two systems interact synergistically and integrate into the central mechanisms of sleep-wake alteration (JS Lin, K Sakai). We also use intracellular recordings, local field potentials and biosensors to study the properties of the cortical network during different types of behavioral states, the respective role of diffuse ascending systems and specific cerebral nuclei, and the mechanisms and effects of extra-synaptic variations of neurotransmitter (S. Crochet, S Marinesco).

From a physio-pathological and translational research standpoint, we work on 1) developing therapeutic approaches for narcolepsy and excessive daytime sleepiness using our knowledge of histaminergic and orexinergic systems (P Franco, JS Lin), 2) investigating the interactions between sleep loss and metabolic disorders in lean subjects and obese patients and in animal models combining sleep/wake and metabolic alterations (K. Spiegel), and 3) identifying new signaling pathways and biomarkers associated with wake thanks to Drosophila molecular genetics (L. Seugnet).

Our work is thus characterized by the use multidisciplinary methodological approaches: electrophysiology and behavior, biosensors, clinical investigations, molecular genetics, and the development of tools for both diagnostic and therapy.

Please click on individual names in the list below for more information.

Methodology

• Electrophysiology (EEG, local field potential, intra and extracellular recordings in behavioral mice and cats)
• Polysomnography in animals (mouse, cat) and humans (adult,child)
• Biosensors (electrochemistry)
• Immunohistochemistry
• Neuro-behavioural testing
• Neuropharmacology
• Cognitive, metabolic and endocrine testing in humans
• Animal models for sleep disorders (mouse, cat)
• Sleep molecular genetics in Drosophila 

Keywords : waking, arousal, sleep, slow wave sleep, REM sleep, cortical activation, posterior hypothalamus, histamine, orexin, sleep-wake disorder, somnolence, waking substance, mesopontine tegmentum, neurophysiology, cat, mouse