TY - JOUR TI - Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit AU - D'Agostino, Giuseppe AU - Lyons, David J AU - Cristiano, Claudia AU - Burke, Luke K AU - Madara, Joseph C AU - Campbell, John N AU - Garcia, Ana Paula AU - Land, Benjamin B AU - Lowell, Bradford B AU - Dileone, Ralph J AU - Heisler, Lora K A2 - Takahashi, Joseph S VL - 5 PY - 2016 DA - 2016/03/14 SP - e12225 C1 - eLife 2016;5:e12225 DO - 10.7554/eLife.12225 UR - https://doi.org/10.7554/eLife.12225 AB - 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 hypothalamus circuit controlling appetite. KW - feeding behavior KW - neuronal circuits KW - neuropeptides JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -