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

GIUSEPPE DAGOSTINO; DAVID J LYONS; CLAUDIA CRISTIANO; LUKE K BURKE; JOSEPH C MADARA; JOHN N CAMPBELL; ANA PAULA GARCÍA; BENJAMIN B LAND; BRADFORD B LOWELL; RALPH J DILEONE; LORA K HEISLER

eLife

eLife Sciences Publications Ltd.

Lugar: Cambridge; Año: 2016

2050-084X

The nucleus of the solitary tract (NTS) is a key gateway for meal-related signalsentering the brain from the periphery. However, the chemical mediators crucial to this processhave 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 bodyweight in mice. Cell-specific anterograde tracing revealed that CCKNTS neurons provide adistinctive innervation of the paraventricular nucleus of the hypothalamus (PVH), with fibers andvaricosities in close apposition to a subset of melanocortin-4 receptor (MC4RPVH) cells, which arealso responsive to CCK. Optogenetic activation of CCKNTS axon terminals within the PVH revealthe satiating function of CCKNTS neurons to be mediated by a CCKNTS-PVH pathway that alsoencodes positive valence. These data identify the functional significance of CCKNTS neurons andreveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.