C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves

Emily Witham; Claudio Comunian; Harkaranveer Ratanpal; Susanne Skora; Manuel Zimmer; Supriya Srinivasan

doi:10.1016/j.celrep.2016.01.052

C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves

Cell Rep. 2016 Feb 23;14(7):1641-1654. doi: 10.1016/j.celrep.2016.01.052. Epub 2016 Feb 11.

Authors

Emily Witham¹, Claudio Comunian², Harkaranveer Ratanpal¹, Susanne Skora³, Manuel Zimmer³, Supriya Srinivasan⁴

Affiliations

¹ 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.
² Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
³ Research Institute of Molecular Pathology IMP, Vienna Biocenter VBC, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
⁴ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue / drug effects*
Adipose Tissue / metabolism
Animals
Caenorhabditis elegans / drug effects*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / antagonists & inhibitors
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Calcium / metabolism
Carbon Dioxide / pharmacology
Cyclic GMP / metabolism
Evoked Potentials, Somatosensory / drug effects*
Evoked Potentials, Somatosensory / genetics
GTP-Binding Protein alpha Subunits / genetics
GTP-Binding Protein alpha Subunits / metabolism
Gene Expression Regulation
Guanylate Cyclase / genetics
Guanylate Cyclase / metabolism
Homeostasis / drug effects*
Homeostasis / genetics
Interoception / drug effects
Ion Channels / genetics
Ion Channels / metabolism
Lipase / antagonists & inhibitors
Lipase / genetics
Lipase / metabolism
Oxygen / pharmacology*
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Sensory Receptor Cells / drug effects*
Sensory Receptor Cells / metabolism
Signal Transduction

Substances

Caenorhabditis elegans Proteins
GTP-Binding Protein alpha Subunits
Ion Channels
RNA, Small Interfering
tax-4 protein, C elegans
Carbon Dioxide
ATGL-1 protein, C elegans
Lipase
GCY-36 protein, C elegans
Guanylate Cyclase
Cyclic GMP
Oxygen
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding