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Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit
Article
Authorship:
D'Agostino, Giuseppe ; Lyons, David J. ; Cristiano, Claudia ; Burke, Luke K. ; Madara, Joseph C. ; Campbell, John N. ; GARCIA, ANA PAULA ; Land, Benjamin B. ; Lowell, Bradford B. ; Dileone, Ralph J. ; Heisler, Lora K.Date:
2016Publishing House and Editing Place:
eLife Sciences Publications LtdMagazine:
eLife, vol. 5 - ISSN 2050-084XeLife Sciences Publications Ltd
ISSN:
2050-084XSummary
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 CCKNTSfiPVH 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.Key Words
CHOLECYSTOKININAPPETITENEUROCIRCUITHYPOTHALAMUS