Synaptic transmission parallels neuromodulation in a central food-intake circuit

Abstract

NeuromedinU is a potent regulator of food intake and activity in mammals. In Drosophila, 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 the Drosophila larval 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.

Article and author information

Author details

  1. Philipp Schlegel

    Department of Molecular Brain Physiology and Behavior, LIMES Institute, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5633-1314
  2. Michael J Texada

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2479-1241
  3. Anton Miroschnikow

    Department of Molecular Brain Physiology and Behavior, LIMES Institute, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Andreas Schoofs

    Department of Molecular Brain Physiology and Behavior, LIMES Institute, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Sebastian Hückesfeld

    Department of Molecular Brain Physiology and Behavior, LIMES Institute, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Marc Peters

    Department of Molecular Brain Physiology and Behavior, LIMES Institute, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Casey M Schneider-Mizell

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9477-3853
  8. Haluk Lacin

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2468-9618
  9. Feng Li

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Richard D Fetter

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. James W Truman

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Albert Cardona

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4941-6536
  13. Michael J Pankratz

    Department of Molecular Brain Physiology and Behavior, LIMES Institute, Bonn, Germany
    For correspondence
    pankratz@uni-bonn.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5458-6471

Funding

Howard Hughes Medical Institute

  • Michael J Texada
  • Casey M Schneider-Mizell
  • Haluk Lacin
  • Feng Li
  • Richard D Fetter
  • James W Truman
  • Albert Cardona

Deutsche Forschungsgemeinschaft

  • Philipp Schlegel
  • Anton Miroschnikow
  • Andreas Schoofs
  • Sebastian Hückesfeld
  • Marc Peters
  • Michael J Pankratz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: April 8, 2016
  2. Accepted: November 14, 2016
  3. Accepted Manuscript published: November 15, 2016 (version 1)
  4. Version of Record published: December 23, 2016 (version 2)
  5. Version of Record updated: June 22, 2021 (version 3)

Copyright

© 2016, Schlegel et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Philipp Schlegel
  2. Michael J Texada
  3. Anton Miroschnikow
  4. Andreas Schoofs
  5. Sebastian Hückesfeld
  6. Marc Peters
  7. Casey M Schneider-Mizell
  8. Haluk Lacin
  9. Feng Li
  10. Richard D Fetter
  11. James W Truman
  12. Albert Cardona
  13. Michael J Pankratz
(2016)
Synaptic transmission parallels neuromodulation in a central food-intake circuit
eLife 5:e16799.
https://doi.org/10.7554/eLife.16799
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