title: A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH.
abstract: Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARCAgRPneurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARCPOMC) neurons are viewed as the counterpoint to ARCAgRPneurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARCAgRPneurons, ARCPOMCneurons are extremely slow in affecting hunger (many hours). Thus, a temporally analogous, rapid ARC satiety pathway does not exist or is presently unidentified. Here we show that glutamate-releasing ARC neurons expressing oxytocin receptor, unlike ARCPOMCneurons, rapidly cause satiety when chemo- or optogenetically manipulated. These glutamatergic ARC projections synaptically converge with GABAergic ARCAgRPprojections on melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVHMC4Rneurons). Transmission across the ARCGlutamatergic→PVHMC4Rsynapse is potentiated by the ARCPOMCneuron-derived MC4R agonist, α-melanocyte stimulating hormone (α-MSH). This excitatory ARC→PVH satiety circuit, and its modulation by α-MSH, provides insight into regulation of hunger and satiety.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Henning
authors.initials: H
authors.lastname: Fenselau
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Campbell
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Anne M J
authors.initials: AM
authors.lastname: Verstegen
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
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, Massachusetts, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bhavik P
authors.initials: BP
authors.lastname: Shah
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Resch
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yael
authors.initials: Y
authors.lastname: Mandelblat-Cerf
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Livneh
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.|Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006815:Hunger / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D055366:Synaptic Potentials / Q000502:physiology*; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D000521:alpha-MSH; D011333:Pro-Opiomelanocortin