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Dynamique du réseau neuronal du sommeil paradoxal – SLEEPNET

Submission summary

Mammalian sleep comprises two major phases, slow-wave sleep (SWS) and paradoxical sleep (PS) also called rapid eye-movement sleep (REM) or dream sleep. These two sleep stages alternate with waking in a cyclic way and a constant order (PS always follows SWS) and rely on a network of cerebral structures that are numerous and distributed throughout the entire neuraxis. Over the past fifty years, lesion, electrophysiological, pharmacological, and more recently molecular biology studies have progressively identified the components of this network. One can thus differentiate SWS structures within the lateral and ventrolateral preoptic area, and PS structures, initially limited to the pons and formed by the dorsal subcoeruleus nucleus and the pontine tegmental nuclei. In addition to the pontine PS structures, we recently identified the hypothalamic neurons containing the MCH peptide (melanin-concentrating hormone) that might be critically involved in PS homeostasis. Sleep structures are anatomically connected to each other and to the waking structures formed by the monoaminergic, cholinergic, and orexinergic (hypocretin) neurons. To date however, the specific role of each of these areas, and their functional interactions at the origin of the alternation of vigilance states remain unknown. This partially explains the lack of a relevant plausible models that can reliably account for the functional organization of this complex network and its dynamics. The prevalence of sleep disorders (hypersomnia, insomnia, narcolepsy/cataplexy) recently highlighted by the French Ministry of Research, now makes even more crucial the comprehensive characterization of the neuronal mechanisms controlling the sleep-wake cycle. Such characterization requires the technical capability to follow-up the activity of the entire network, or by default of its key structures. This approach is now made possible in animals thanks to multi-electrodes implants and multi-channel recording systems allowing, not only to simultaneously monitor spike signals and local field potential within multiple distant structures, but also to assess the functional interactions between them. Still inexistent in France, the multi-site electrophysiological approach is the one that we propose to introduce in order to elucidate the functional organization of the sleep network and its dynamics. This innovative approach will first be used to study the ponto-medullar structures responsible for the onset and maintenance of PS, and then be extended to the hypothalamic structures involved in the homeostatic regulation of PS. Quantitative analyses based on peri-event time histogram will be applied to single unit activity of multiple neurons to assess the chronology of critical events taking place in the network at the transitions between the sleep stages. We will then attempt to determine the mechanisms underlying this chronology by investigating the correlations and synchronizations of spike activity and local field potential signals from the different neuronal populations. Altogether, this data should allow us to progress significantly in the knowledge of the neuronal mechanisms of the normal sleep-wake cycle, an essential step towards the understanding of sleep disorders. Centered on the dynamics of the network responsible for the sleep-wake cycle, this project fits totally into the main topic of the host laboratory. The achievement of this project involves the expertise of young research scientists, Damien Gervasoni and Shih-Chieh Lin, experts in multi-electrode recordings in behaving Rats and analysis of neural ensembles, and Christelle Peyron, a specialist in hypothalamic peptidergic systems and of narcolepsy/cataplexy. These domains of expertise will reinforce the bundle of competence and techniques already available (extra- and intracellular recordings in Rodents, track-tracing, functional anatomy studies and proteogenomics, DNA chips). The financial support from the 'ANR' represents a unique opportunity to purchase promptly the equipment for MUMS recordings, essential to run this project, and to promote later on the creation of a center of excellence in the investigation of complex neuronal networks. Beyond the physiology of sleep, our experimental approach should also offer numerous theoretical and experimental prospects in the Neurophysiology of integrated systems.

Project coordination

Damien GERVASONI (Université)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Help of the ANR 167,000 euros
Beginning and duration of the scientific project: - 48 Months

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