title: The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarization.
abstract: Wakefulness depends on the activity of hypocretin-orexin neurons because their lesion results in narcolepsy. How these neurons maintain their activity to promote wakefulness is not known. Here, by recording for the first time from hypocretin-orexin neurons and comparing their properties with those of neurons expressing melanin-concentrating hormone, we show that hypocretin-orexin neurons are in an intrinsic state of membrane depolarization that promotes their spontaneous activity. We propose that wakefulness and associated energy expenditure thus depend on that property, which allows the hypocretin-orexin neurons to maintain a tonic excitatory influence on the central arousal and peripheral sympathetic systems.
authors.affiliation: Département de Physiologie, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Eggermann
authors.forename: Laurence
authors.initials: L
authors.lastname: Bayer
authors.forename: Mauro
authors.initials: M
authors.lastname: Serafin
authors.forename: Benoît
authors.initials: B
authors.lastname: Saint-Mleux
authors.forename: Laurent
authors.initials: L
authors.lastname: Bernheim
authors.forename: Danièle
authors.initials: D
authors.lastname: Machard
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Jones
authors.forename: Michel
authors.initials: M
authors.lastname: Mühlethaler
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001143:Arousal / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D000068797:Orexins; D018408:Patch-Clamp Techniques; D010907:Pituitary Hormones / Q000378:metabolism; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014851:Wakefulness / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C019463:melanin-concentrating hormone; D009532:Nickel; D002794:Choline