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Mapping of hypothalamic neurons implicated in sleep and metabolic control.

English title Mapping of hypothalamic neurons implicated in sleep and metabolic control.
Applicant Adamantidis Antoine
Number 188761
Funding scheme Project funding (Div. I-III)
Research institution Universitätsklinik für Neurologie Inselspital Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2020 - 31.12.2023
Approved amount 700'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Physiology : other topics

Keywords (6)

Hypothalamus; Neural circuits; Sleep; Optogenetics; goal-directed behaviour; Wake

Lay Summary (French)

Lead
Explorer le role du sommeil dans la regulation du metabolisme et les comportements motives.
Lay summary
Le sommeil est un besoin biologique primaire et essentiel pour les vertébrés supérieurs, et des états semblables au sommeil ont été identifiés chez les vertébrés inférieurs. Alors que les fonctions du sommeil sont encore un sujet de débat et peuvent inclure la consolidation de la mémoire, la clairance cérébrale et la plasticité cérébrale, les mécanismes neurobiologiques contrôlant l'architecture veille-sommeil et les fonctions du sommeil restent largement inconnus. Chez l'homme, de legeres perturbations du sommeil ont des conséquences dramatiques, notamment des troubles cognitifs et un déséquilibre métabolique souvent associés au diabète et à l'obésité. L’hypothalamus est susceptible de jouer un rôle dans l’association «sommeil-métabolisme» car il contient des circuits neuronaux impliqués dans les états veille-sommeil et les comportements axés sur les objectifs. Dans ce projet, nous étudierons la contribution spécifique du sommeil aux mécanismes qui sous-tendent le controle hypothalamique  de l'homéostasie énergétique et d'autres fonctions exécutives telles que les comportements motives.
Direct link to Lay Summary Last update: 18.12.2019

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
156156 Optogenetic dissection of hypothalamic regulation of sleep-wake states 01.01.2015 Project funding (Div. I-III)

Abstract

BackgroundSleep is a primary and essential biological need for higher vertebrates, and sleep-like states have been demonstrated in lower vertebrates. While the functions of sleep are still a matter of debate and may include memory consolidation, brain clearance and brain plasticity, the basic neurobiological mechanisms controlling sleep-wake architecture and sleep functions remain largely unknown. In humans, subtle sleep perturbations have dramatic consequences, including cognitive impairments and metabolic imbalance often associated with diabetes and obesity. The hypothalamus is likely to play a role in the ‘Sleep-Metabolism’ association because it contains neuronal circuits implicated in sleep-wake states and goal-oriented behaviours1,2. The specific contribution of these hypothalamic network mechanisms to the maintenance of energy homeostasis and other executive functions such as goal-directed behaviours remains an open question with direct implications for neuro-psychiatric diseases. Thus, our goal is to better understand the wiring, dynamics and plasticity of hypothalamic sleep-wake circuits, and their implication in sleep architecture and sleep functions including cognition and goal-directed behaviours. Rationale & Preliminary data The elaboration of behavioural strategies to meet homeostatic needs in an ever-changing environment is a major challenge for the mammalian brain. The lateral hypothalamus (LH) plays a key role in the integration of hormonal, metabolic, circadian, and motivational signals into coherent goal-directed behaviours and proper sleep-wake states. We and others have identified subpopulations of inhibitory neurons in the LH that controls wakefulness/arousal, rapid eye-movement (REM) sleep, or appetitive/consummatory behaviours in mice. Yet, how LH neuronal populations compute both sleep and metabolic functions remains largely unknown. Objectives & HypothesisOur overarching hypothesis is that 1) LH encompasses neuron populations that are implicated in either REM sleep structure or in REM sleep function(s); and 2) reactivation of LH neurons encoding goal-oriented behaviours during a sleep-specific state, including REM sleep, provides an off-line mechanism for the fine-tuning of circuit activity implicated in homeostasis. To test this hypothesis, we will characterize the stability of inhibitory and excitatory LH neuron clusters encoding sleep-wake states; study the reactivation pattern of wake-active LH neurons during sleep; and, characterize REM-sleep dependent tuning of LH neuron excitability using a combination of optical and electrophysiological technologies Expected results & ImpactIn addition to providing important clues about the brain mechanism of REM sleep, completion of this research project will shed light on the dynamics and plasticity of neuronal network encoding sleep-wake states and appetitive/consummatory behaviours in the hypothalamus. It will further identify the long-sought multitasking functions of LH circuits in sleep and metabolism.
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