Synaptic transmission parallels neuromodulation in a central food-intake circuit

Philipp Schlegel, Michael J. Texada, Anton Miroschnikow, Andreas Schoofs, Sebastian Hückesfeld, Marc Peters, Casey M. Schneider-Mizell, Haluk Lacin, Feng Li, Richard D. Fetter, James W. Truman, Albert Cardona, Michael J. Pankratz

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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.

Original languageEnglish
Article numbere16799
JournaleLife
Volume5
Issue numberNOVEMBER2016
DOIs
StatePublished - Nov 15 2016

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