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Science 2 April 2004:
Vol. 304. no. 5667, pp. 110 - 115
DOI: 10.1126/science.1089459
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Reports

Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin

Shirly Pinto,1* Aaron G. Roseberry,1* Hongyan Liu,1* Sabrina Diano,3 Marya Shanabrough,3 Xiaoli Cai,1,2 Jeffrey M. Friedman,1,2{dagger} Tamas L. Horvath3,4{dagger}

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.

1 Laboratory of Molecular Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
2 Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
3 Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
4 Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520, USA.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: friedj{at}mail.rockefeller.edu (J.M.F.); tamas.horvath{at}yale.edu (T.L.H.)

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