Abstract
Neuromedin U (NMU) is a potent regulator of food intake and activity in mammals. While some downstream targets of NMU have been localized, connectivity of the neural circuits employing this neuropeptide is largely unknown. In Drosophila, neurons producing the homologous neuropeptide hugin regulate feeding and locomotion in a similar manner and project to structures of the central nervous system analogous to those in which NMU is found. Here, we use EM reconstruction and receptor expression analysis to map the connectome of hugin-producing neurons in the Drosophila larval central nervous system. We show that hugin-producing neurons establish distinct units that are reciprocally connected and share connectivity motifs. One of these units employs fast synaptic transmission as well as neuromodulation to target neuroendocrine cells (NSCs) of the pars intercerebralis, the Drosophila homolog of the hypothalamus. These NSCs produce CRH- and insulin-like peptides, which are homologs of downstream targets of NMU. Furthermore, most of the hugin-producing neurons, including those that target the NSCs, receive inputs from chemosensory neurons in the subesophageal zone, the brain stem analog in Drosophila. Our data positions hugin neurons as part of a novel sensory-to-endocrine network that reflects the way NMU operates in mammals. We propose that the hugin neurons interconnecting chemosensory and neuroendocrine organs are part of a physiological control system that has been conserved not only at functional and molecular levels, but at the network architecture level as well.
