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Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9489-E9498. doi: 10.1073/pnas.1802237115. Epub 2018 Sep 17.

Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding.

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Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109.
Department of Biological Sciences, Columbia University, New York, NY 10027.
Department of Bioengineering, Stanford University, Stanford, CA 94305.
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109;


Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.


agouti-related protein; arcuate nucleus; feeding; proopiomelanocortin; satiety

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