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

Version 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.

Metrics

  • 4,555
    views
  • 986
    downloads
  • 116
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.16799

Further reading

    1. Neuroscience
    Kenta Abe, Yuki Kambe ... Tatsuo Sato
    Research Article

    Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

    1. Neuroscience
    Baiwei Liu, Zampeta-Sofia Alexopoulou, Freek van Ede
    Research Article

    Working memory enables us to bridge past sensory information to upcoming future behaviour. Accordingly, by its very nature, working memory is concerned with two components: the past and the future. Yet, in conventional laboratory tasks, these two components are often conflated, such as when sensory information in working memory is encoded and tested at the same location. We developed a task in which we dissociated the past (encoded location) and future (to-be-tested location) attributes of visual contents in working memory. This enabled us to independently track the utilisation of past and future memory attributes through gaze, as observed during mnemonic selection. Our results reveal the joint consideration of past and future locations. This was prevalent even at the single-trial level of individual saccades that were jointly biased to the past and future. This uncovers the rich nature of working memory representations, whereby both past and future memory attributes are retained and can be accessed together when memory contents become relevant for behaviour.