title: Cholinergic neurons in the dorsomedial hypothalamus regulate food intake.
abstract: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake.
  
  
  
  To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice. We also generated transgenic mice expressing channelrhodopsins in cholinergic neurons with the Cre-LoxP technique. To delete theChatgene exclusively in the DMH, we injected an AAV carrying a Cre recombinase transgene into the DMH of floxed ChAT mice. Food intake was measured with and without selective stimulation of DMH cholinergic neurons.
  
  
  
  Mice lacking theChatgene in the DMH show reduced body weight as compared to control. Chemogenetic activation of DMH cholinergic neurons promotes food intake. This orexigenic effect is further supported by experiments of optogenetic stimulation of DMH cholinergic neurons. DMH cholinergic neurons innervate pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (ARC). Treatment with acetylcholine (ACh) enhances GABAergic inhibitory transmission to ARC POMC neurons that is blocked by the muscarinic receptor antagonist. Direct activation of cholinergic fibers in the ARC readily stimulates food intake that is also abolished by the muscarinic receptor antagonist.
  
  
  
  ACh released from DMH cholinergic neurons regulates food intake and body weight. This effect is mediated in part through regulation of ARC POMC neurons. Activation of muscarinic receptors on GABAergic axon terminals enhances inhibitory tone to ARC POMC neurons. Hence, this novel DMHACh→ ARCPOMCpathway plays an important role in the control of food intake and body weight.
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, NY, USA.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, NY, USA; Department of Physiology, College of Medicine, Gyeongsang National University, Jinju, South Korea.
authors.forename: Dong Kun
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, NY, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, NY, USA. Electronic address: young-hwan.jo@einstein.yu.edu.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Jo
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001835:Body Weight; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism; D004435:Eating / Q000235:genetics / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000378:metabolism / Q000502:physiology*; D019426:Integrases; D020738:Leptin / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism
chemical_list: D020738:Leptin; D011333:Pro-Opiomelanocortin; D002795:Choline O-Acetyltransferase; C045073:Cre recombinase; D019426:Integrases
keywords: Acetylcholine; Hypothalamus; Muscarinic; Nicotinic; Obesity; POMC