title: Rapid rewiring of arcuate nucleus feeding circuits by leptin.
abstract: The fat-derived hormone leptin regulates energy balance in part by modulating the activity of neuropeptide Y and proopiomelanocortin neurons in the hypothalamic arcuate nucleus. To study the intrinsic activity of these neurons and their responses to leptin, we generated mice that express distinct green fluorescent proteins in these two neuronal types. Leptin-deficient (ob/ob) mice differed from wild-type mice in the numbers of excitatory and inhibitory synapses and postsynaptic currents onto neuropeptide Y and proopiomelanocortin neurons. When leptin was delivered systemically to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours before leptin's effect on food intake. These data suggest that leptin-mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's behavioral effects.
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Shirly
authors.initials: S
authors.lastname: Pinto
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Roseberry
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
authors.forename: Marya
authors.initials: M
authors.lastname: Shanabrough
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cai
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D004435:Eating; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials; D005247:Feeding Behavior / Q000187:drug effects; D054439:Ghrelin; D018698:Glutamic Acid / Q000032:analysis; D049452:Green Fluorescent Proteins; D066298:In Vitro Techniques; D020738:Leptin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology; D018408:Patch-Clamp Techniques; D036361:Peptide Hormones / Q000494:pharmacology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000032:analysis; D013569:Synapses / Q000737:chemistry / Q000648:ultrastructure; D013779:Tetrodotoxin / Q000494:pharmacology; D019076:Transgenes; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D054439:Ghrelin; D020738:Leptin; D008164:Luminescent Proteins; D009478:Neuropeptide Y; D036361:Peptide Hormones; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011333:Pro-Opiomelanocortin