title: Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus.
abstract: OBJECTIVE
  The dorsomedial hypothalamus (DMH) has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART), cholecystokinin (CCK), leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques.
  
  
  METHODS
  We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp.
  
  
  RESULTS
  Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN), where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake.
  
  
  CONCLUSIONS
  DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 320-0498, Japan.
authors.forename: Zesemdorj
authors.initials: Z
authors.lastname: Otgon-Uul
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 320-0498, Japan.
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Suyama
authors.affiliation: Photon Science Center of the University of Tokyo, Department of Electrical Engineering of the University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onodera
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 320-0498, Japan. Electronic address: tyada@jichi.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
keywords: Dorsomedial hypothalamus; Feeding; GABAergic neuron; Glucose; Leptin; Optogenetics