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

Giuseppe D'Agostino (Corresponding Author), David J. Lyons, Claudia Cristiano, Luke K. Burke, Joseph C. Madara, John N. Campbell, Ana Paula Garcia, Benjamin B. Land, Bradford B. Lowell, Ralph J. Dileone, Lora K. Heisler (Corresponding Author)

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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 (CCKNTS) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCKNTS 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 (MC4RPVH) cells, which are also responsive to CCK. Optogenetic activation of CCKNTS axon terminals within the PVH reveal the satiating function of CCKNTS neurons to be mediated by a CCKNTS→PVH pathway that also encodes positive valence. These data identify the functional significance of CCKNTS neurons and reveal a sufficient and discrete NTS to hypothalamic circuit controlling appetite.
Original languageEnglish
Article number12225
Pages (from-to)1-15
Number of pages15
JournaleLife
Volume5
DOIs
Publication statusPublished - 14 Mar 2016

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D'Agostino, G., Lyons, D. J., Cristiano, C., Burke, L. K., Madara, J. C., Campbell, J. N., ... Heisler, L. K. (2016). Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. eLife, 5, 1-15. [12225]. https://doi.org/10.7554/eLife.12225