title: A cholinergic basal forebrain feeding circuit modulates appetite suppression.
abstract: Atypical food intake is a primary cause of obesity and other eating and metabolic disorders. Insight into the neural control of feeding has previously focused mainly on signalling mechanisms associated with the hypothalamus, the major centre in the brain that regulates body weight homeostasis. However, roles of non-canonical central nervous system signalling mechanisms in regulating feeding behaviour have been largely uncharacterized. Acetylcholine has long been proposed to influence feeding owing in part to the functional similarity between acetylcholine and nicotine, a known appetite suppressant. Nicotine is an exogenous agonist for acetylcholine receptors, suggesting that endogenous cholinergic signalling may play a part in normal physiological regulation of feeding. However, it remains unclear how cholinergic neurons in the brain regulate food intake. Here we report that cholinergic neurons of the mouse basal forebrain potently influence food intake and body weight. Impairment of cholinergic signalling increases food intake and results in severe obesity, whereas enhanced cholinergic signalling decreases food consumption. We found that cholinergic circuits modulate appetite suppression on downstream targets in the hypothalamus. Together our data reveal the cholinergic basal forebrain as a major modulatory centre underlying feeding behaviour.
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Herman
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Ortiz-Guzman
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kochukov
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Isabella
authors.initials: I
authors.lastname: Herman
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Quast
authors.affiliation: Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Patel
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Burak
authors.initials: B
authors.lastname: Tepe
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Carlson
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ung
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Selever
authors.affiliation: Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.|Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Arenkiel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D066187:Basal Forebrain / Q000166:cytology* / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D016923:Cell Death; D002795:Choline O-Acetyltransferase / Q000172:deficiency; D018679:Cholinergic Agonists; D059329:Cholinergic Neurons / Q000378:metabolism* / Q000473:pathology; D004435:Eating / Q000502:physiology / Q000523:psychology; D005247:Feeding Behavior / Q000502:physiology* / Q000523:psychology; D005260:Female; D006706:Homeostasis; D006963:Hyperphagia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009538:Nicotine / Q000378:metabolism; D009765:Obesity / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011950:Receptors, Cholinergic / Q000378:metabolism; D012528:Satiety Response / Q000502:physiology*
chemical_list: D018679:Cholinergic Agonists; D011950:Receptors, Cholinergic; D009538:Nicotine; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine