Rapid rewiring of arcuate nucleus feeding circuits by leptin.
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.
Pinto
Shirly
S
Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Roseberry
Aaron G
AG
Liu
Hongyan
H
Diano
Sabrina
S
Shanabrough
Marya
M
Cai
Xiaoli
X
Friedman
Jeffrey M
JM
Horvath
Tamas L
TL
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
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