D'Agostino, GiuseppeLyons, David JCristiano, ClaudiaBurke, Luke KMadara, JosephCampbell, JohnGarcia, Ana PaulaLand, Benjamin BLowell, BradfordDileone, Ralph JHeisler, Lora K2016-06-142016D'Agostino, G., D. J. Lyons, C. Cristiano, L. K. Burke, J. C. Madara, J. N. Campbell, A. P. Garcia, et al. 2016. “Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.” eLife 5 (1): e12225. doi:10.7554/eLife.12225. http://dx.doi.org/10.7554/eLife.12225.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27320198The 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 hypothalamus circuit controlling appetite. DOI: http://dx.doi.org/10.7554/eLife.12225.001en-USShort Reportfeeding behaviorneuronal circuitsneuropeptidesMouseJournal Article2016-06-1410.7554/eLife.12225