title: Electrical inhibition of identified anorexigenic POMC neurons by orexin/hypocretin.
abstract: Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus (ARC) suppress appetite, and lack of POMC-derived peptides or electrical silencing of POMC neurons causes obesity. ARC POMC neurons are surrounded by nerve terminals containing the wakefulness-promoting peptides orexins/hypocretins, but whether orexin affects their electrical activity has not been tested directly. Here we identify living ARC POMC cells in mouse brain slices by targeted expression of green fluorescent protein. Using whole-cell patch-clamp recordings, we show that orexin suppresses the spontaneous action potential firing of these neurons. Orexin-induced inhibition involves membrane hyperpolarization, a decreased excitatory synaptic drive, and an increased frequency of GABAergic inputs. Our results suggest a reduction in the electrical activity of ARC POMC neurons, which is mediated by changes in presynaptic inputs, contributes to the appetite-enhancing action of orexins.
authors.affiliation: University Laboratory of Physiology, Oxford OX1 3PT, United Kingdom.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Ma
authors.forename: Lejla
authors.initials: L
authors.lastname: Zubcevic
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
authors.forename: Denis
authors.initials: D
authors.lastname: Burdakov
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D010852:Picrotoxin; D011333:Pro-Opiomelanocortin