title: Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism.
abstract: Sleep-active neurons located in the ventrolateral preoptic nucleus (VLPO) play a crucial role in the induction and maintenance of slow-wave sleep (SWS). However, the cellular and molecular mechanisms responsible for their activation at sleep onset remain poorly understood. Here, we test the hypothesis that a rise in extracellular glucose concentration in the VLPO can promote sleep by increasing the activity of sleep-promoting VLPO neurons. We find that infusion of a glucose concentration into the VLPO of mice promotes SWS and increases the density of c-Fos-labeled neurons selectively in the VLPO. Moreover, we show in patch-clamp recordings from brain slices that VLPO neurons exhibiting properties of sleep-promoting neurons are selectively excited by glucose within physiological range. This glucose-induced excitation implies the catabolism of glucose, leading to a closure of ATP-sensitive potassium (KATP) channels. The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status. Together, these results provide evidence that glucose may participate in the mechanisms of SWS promotion and/or consolidation.
  
  
  CONCLUSIONS
  Although the brain circuitry underlying vigilance states is well described, the molecular mechanisms responsible for sleep onset remain largely unknown. Combining in vitro and in vivo experiments, we demonstrate that glucose likely contributes to sleep onset facilitation by increasing the excitability of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO). We find here that these neurons integrate energetic signals such as ambient glucose directly to regulate vigilance states accordingly. Glucose-induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. This novel mechanism regulating the activity of VLPO neurons reinforces the fundamental and intimate link between sleep and metabolism.
authors.affiliation: Brain Plasticity Unit, Sleep Neuronal Networks Team, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8249, 75005 Paris, France, Ecole Supérieure de Physique et de Chimie Industrielles ParisTech, 75005 Paris, France, Physiopathologie des Réseaux Neuronaux Responsables du Cycle Veille-Sommeil Team, INSERM, U1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon Neuroscience Research Center, 69372 Lyon, France, and University Lyon 1, 69000 Lyon, France.
authors.forename: Christophe
authors.identifier: http://orcid.org/0000-0002-9150-0654
authors.initials: C
authors.lastname: Varin
authors.affiliation: Brain Plasticity Unit, Sleep Neuronal Networks Team, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8249, 75005 Paris, France, Ecole Supérieure de Physique et de Chimie Industrielles ParisTech, 75005 Paris, France.
authors.forename: Armelle
authors.identifier: http://orcid.org/0000-0003-1085-5929
authors.initials: A
authors.lastname: Rancillac
authors.affiliation: Brain Plasticity Unit, Sleep Neuronal Networks Team, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8249, 75005 Paris, France, Ecole Supérieure de Physique et de Chimie Industrielles ParisTech, 75005 Paris, France.
authors.forename: Hélène
authors.identifier: http://orcid.org/0000-0002-3231-8369
authors.initials: H
authors.lastname: Geoffroy
authors.affiliation: Physiopathologie des Réseaux Neuronaux Responsables du Cycle Veille-Sommeil Team, INSERM, U1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon Neuroscience Research Center, 69372 Lyon, France, and University Lyon 1, 69000 Lyon, France.
authors.forename: Sébastien
authors.identifier: http://orcid.org/0000-0001-7271-5468
authors.initials: S
authors.lastname: Arthaud
authors.affiliation: Physiopathologie des Réseaux Neuronaux Responsables du Cycle Veille-Sommeil Team, INSERM, U1028, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5292, Lyon Neuroscience Research Center, 69372 Lyon, France, and University Lyon 1, 69000 Lyon, France.
authors.forename: Patrice
authors.identifier: http://orcid.org/0000-0003-1211-8631
authors.initials: P
authors.lastname: Fort
authors.affiliation: Brain Plasticity Unit, Sleep Neuronal Networks Team, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8249, 75005 Paris, France, Ecole Supérieure de Physique et de Chimie Industrielles ParisTech, 75005 Paris, France, thierry.gallopin@espci.fr.
authors.forename: Thierry
authors.identifier: http://orcid.org/0000-0002-9741-3738
authors.initials: T
authors.lastname: Gallopin
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D058256:Brain Waves / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology* / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D013549:Sweetening Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D003373:Coumaric Acids; D051274:Glucose Transporter Type 3; D049990:Membrane Transport Modulators; D016760:Proto-Oncogene Proteins c-fos; D013549:Sweetening Agents; C007175:alpha-cyano-4-hydroxycinnamate; D003847:Deoxyglucose; D005947:Glucose; D009638:Norepinephrine
keywords: glucose; homeostasis; hypothalamus; polysomnography; preoptic nucleus; sleep