title: Synaptic transmission parallels neuromodulation in a central food-intake circuit.
abstract: NeuromedinU is a potent regulator of food intake and activity in mammals. InDrosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner. Here, we use EM-based reconstruction to generate the entire connectome of hugin-producing neurons in theDrosophilalarval CNS. We demonstrate that hugin neurons use synaptic transmission in addition to peptidergic neuromodulation and identify acetylcholine as a key transmitter. Hugin neuropeptide and acetylcholine are both necessary for the regulatory effect on feeding. We further show that subtypes of hugin neurons connect chemosensory to endocrine system by combinations of synaptic and peptide-receptor connections. Targets include endocrine neurons producing DH44, a CRH-like peptide, and insulin-like peptides. Homologs of these peptides are likewise downstream of neuromedinU, revealing striking parallels in flies and mammals. We propose that hugin neurons are part of an ancient physiological control system that has been conserved at functional and molecular level.
authors.affiliation: Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Philipp
authors.identifier: http://orcid.org/0000-0002-5633-1314
authors.initials: P
authors.lastname: Schlegel
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0003-2479-1241
authors.initials: MJ
authors.lastname: Texada
authors.affiliation: Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Miroschnikow
authors.affiliation: Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schoofs
authors.affiliation: Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hückesfeld
authors.affiliation: Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Peters
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Casey M
authors.identifier: http://orcid.org/0000-0001-9477-3853
authors.initials: CM
authors.lastname: Schneider-Mizell
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Haluk
authors.identifier: http://orcid.org/0000-0003-2468-9618
authors.initials: H
authors.lastname: Lacin
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Fetter
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: James W
authors.initials: JW
authors.lastname: Truman
authors.affiliation: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Albert
authors.identifier: http://orcid.org/0000-0003-4941-6536
authors.initials: A
authors.lastname: Cardona
authors.affiliation: Department of Molecular Brain Physiology and Behavior, LIMES Institute, University of Bonn, Bonn, Germany.
authors.forename: Michael J
authors.identifier: http://orcid.org/0000-0001-5458-6471
authors.initials: MJ
authors.lastname: Pankratz
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004330:Drosophila / Q000033:anatomy & histology* / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D004435:Eating; D007814:Larva / Q000033:anatomy & histology / Q000502:physiology; D008854:Microscopy, Electron; D009434:Neural Pathways / Q000033:anatomy & histology*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D029721:Drosophila Proteins; C515386:Hug protein, Drosophila; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000109:Acetylcholine
keywords: D. melanogaster; acetylcholine; co-transmission; endocrine; hugin; neuromedin; neuropeptides; neuroscience