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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.

Author information

1
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
2
Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
3
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
4
Department of Psychiatry, Yale University School of Medicine, New Haven, United States.

Abstract

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.

KEYWORDS:

feeding behavior; mouse; neuronal circuits; neuropeptides; neuroscience

Comment in

PMID:
26974347
PMCID:
PMC4861598
DOI:
10.7554/eLife.12225
[Indexed for MEDLINE]
Free PMC Article

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