RT Journal Article SR Electronic T1 Synaptic Transmission Parallels Neuromodulation in a Central Food-Intake Circuit JF bioRxiv FD Cold Spring Harbor Laboratory SP 044990 DO 10.1101/044990 A1 Philipp Schlegel A1 Michael J. Texada A1 Anton Miroschnikow A1 Andreas Schoofs A1 Sebastian Hückesfeld A1 Marc Peters A1 Casey M. Schneider-Mizell A1 Haluk Lacin A1 Feng Li A1 Richard D. Fetter A1 James W. Truman A1 Albert Cardona A1 Michael J. Pankratz YR 2016 UL http://biorxiv.org/content/early/2016/09/29/044990.abstract AB 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 a physiological control system that has been conserved at functional, molecular and network architecture level.