title: Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit.
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 (CCK(NTS)) is responsive to nutritional state and that their activation reduces appetite and body weight in mice. Cell-specific anterograde tracing revealed that CCK(NTS) 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 (MC4R(PVH)) cells, which are also responsive to CCK. Optogenetic activation of CCK(NTS) axon terminals within the PVH reveal the satiating function of CCK(NTS) neurons to be mediated by a CCK(NTS)→PVH pathway that also encodes positive valence. These data identify the functional significance of CCK(NTS) neurons and reveal a sufficient and discrete NTS to hypothalamus circuit controlling appetite.
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.|Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Agostino
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lyons
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Claudia
authors.identifier: 0000-0002-4806-1764
authors.initials: C
authors.lastname: Cristiano
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Luke K
authors.initials: LK
authors.lastname: Burke
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Madara
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
authors.forename: John N
authors.initials: JN
authors.lastname: Campbell
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Garcia
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, United States.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Land
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, United States.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Dileone
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.|Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lora K
authors.identifier: 0000-0002-7731-1419
authors.initials: LK
authors.lastname: Heisler
mesh_terms: D000818:Animals; D001066:Appetite; D001931:Brain Mapping; D002766:Cholecystokinin / Q000378:metabolism*; D051379:Mice; D009434:Neural Pathways / Q000033:anatomy & histology*; D062308:Optogenetics; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D017552:Solitary Nucleus / Q000502:physiology*
chemical_list: D002766:Cholecystokinin
keywords: feeding behavior; mouse; neuronal circuits; neuropeptides; neuroscience