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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.

Pubmed ID: 15064421


  • Pinto S
  • Roseberry AG
  • Liu H
  • Diano S
  • Shanabrough M
  • Cai X
  • Friedman JM
  • Horvath TL


Science (New York, N.Y.)

Publication Data

April 2, 2004

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK060711
  • Agency: NIDDK NIH HHS, Id: F32DK61176
  • Agency: NINDS NIH HHS, Id: F32NS046921
  • Agency: NIDDK NIH HHS, Id: R01 DK041096
  • Agency: NIDDK NIH HHS, Id: R01 DK061619
  • Agency: NCRR NIH HHS, Id: RR014451

Mesh Terms

  • Animals
  • Arcuate Nucleus of Hypothalamus
  • Body Weight
  • Eating
  • Evoked Potentials
  • Excitatory Postsynaptic Potentials
  • Feeding Behavior
  • Ghrelin
  • Glutamic Acid
  • Green Fluorescent Proteins
  • In Vitro Techniques
  • Leptin
  • Luminescent Proteins
  • Mice
  • Mice, Obese
  • Mice, Transgenic
  • Neuronal Plasticity
  • Neurons
  • Neuropeptide Y
  • Patch-Clamp Techniques
  • Peptide Hormones
  • Pro-Opiomelanocortin
  • Recombinant Fusion Proteins
  • Synapses
  • Tetrodotoxin
  • Transgenes
  • gamma-Aminobutyric Acid