title: C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves.
abstract: It is known that internal physiological state, or interoception, influences CNS function and behavior. However, the neurons and mechanisms that integrate sensory information with internal physiological state remain largely unknown. Here, we identify C. elegans body cavity neurons called URX(L/R) as central homeostatic sensors that integrate fluctuations in oxygen availability with internal metabolic state. We show that depletion of internal body fat reserves increases the tonic activity of URX neurons, which influences the magnitude of the evoked sensory response to oxygen. These responses are integrated via intracellular cGMP and Ca(2+). The extent of neuronal activity thus reflects the balance between the perception of oxygen and available fat reserves. The URX homeostatic sensor ensures that neural signals that stimulate fat loss are only deployed when there are sufficient fat reserves to do so. Our results uncover an interoceptive neuroendocrine axis that relays internal state information to the nervous system.
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Dorris Neuroscience Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Witham
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Comunian
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Dorris Neuroscience Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Harkaranveer
authors.initials: H
authors.lastname: Ratanpal
authors.affiliation: Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Skora
authors.affiliation: Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zimmer
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Dorris Neuroscience Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: supriya@scripps.edu.
authors.forename: Supriya
authors.initials: S
authors.lastname: Srinivasan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects* / Q000235:genetics; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects* / Q000235:genetics; D065812:Interoception / Q000187:drug effects; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008049:Lipase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D044385:GTP-Binding Protein alpha Subunits; D007473:Ion Channels; D034741:RNA, Small Interfering; C102184:tax-4 protein, C elegans; D002245:Carbon Dioxide; C534632:ATGL-1 protein, C elegans; D008049:Lipase; C511349:GCY-36 protein, C elegans; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D010100:Oxygen; D002118:Calcium