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Elife. 2016 Mar 14;5. pii: e12225. doi: 10.7554/eLife.12225.

Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.

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Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
Department of Psychiatry, Yale University School of Medicine, New Haven, United States.


The nucleus of the solitary tract (NTS) is a key gateway for meal-related signals entering the brain from the periphery. However, the chemical mediators crucial to this process have not been fully elucidated. We reveal that a subset of NTS neurons containing cholecystokinin (CCK(NTS)) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCK(NTS) neurons provide a distinctive innervation of the paraventricular nucleus of the hypothalamus (PVH), with fibers and varicosities in close apposition to a subset of melanocortin-4 receptor (MC4R(PVH)) cells, which are also responsive to CCK. Optogenetic activation of CCK(NTS) axon terminals within the PVH reveal the satiating function of CCK(NTS) neurons to be mediated by a CCK(NTS)→PVH pathway that also encodes positive valence. These data identify the functional significance of CCK(NTS) neurons and reveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.


feeding behavior; mouse; neuronal circuits; neuropeptides; neuroscience

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