Vasopressin/Oxytocin-Related Signaling Regulates Gustatory Associative Learning in C. elegans

Social Neuropeptides in Nematodes The neuropeptides oxytocin and vasopressin stimulate maternal, reproductive, aggressive, and affiliative behaviors in mammals. They are implicated in behaviors ranging from ewe-lamb bonding in sheep to pair bonding in voles (see the Perspective by Emmons). Now, Garrison et al. (p. 540) and Beets et al. (p. 543) extend the evolutionary reach of these social neuropeptides to the invertebrate nematode worm, Caenorhabditis elegans. A similar neuropeptide was found to function in mating and also to modulate salt-taste preference, based on prior experience, suggesting an ancient role in associative learning. Nematode neuropeptides and their G protein–coupled receptors support behavioral responses to salt. Vasopressin- and oxytocin-related neuropeptides are key regulators of animal physiology, including water balance and reproduction. Although these neuropeptides also modulate social behavior and cognition in mammals, the mechanism for influencing behavioral plasticity and the evolutionary origin of these effects are not well understood. Here, we present a functional vasopressin- and oxytocin-like signaling system in the nematode Caenorhabditis elegans. Through activation of its receptor NTR-1, a vasopressin/oxytocin-related neuropeptide, designated nematocin, facilitates the experience-driven modulation of salt chemotaxis, a type of gustatory associative learning in C. elegans. Our study suggests that vasopressin and oxytocin neuropeptides have ancient roles in modulating sensory processing in neural circuits that underlie behavioral plasticity.

[1]  A. Izquierdo,et al.  Impaired reward learning and intact motivation after serotonin depletion in rats , 2012, Behavioural Brain Research.

[2]  Oliver Hobert,et al.  PCR fusion-based approach to create reporter gene constructs for expression analysis in transgenic C. elegans. , 2002, BioTechniques.

[3]  P. Sternberg,et al.  Two neuronal G proteins are involved in chemosensation of the Caenorhabditis elegans Dauer-inducing pheromone. , 1997, Genetics.

[4]  S. Brenner.  The genetics of Caenorhabditis elegans. , 1974, Genetics.

[5]  Liliane Schoofs,et al.  Discovery of a cholecystokinin-gastrin-like signaling system in nematodes. , 2008, Endocrinology.

[6]  R. Beeman,et al.  Vasopressin-like peptide and its receptor function in an indirect diuretic signaling pathway in the red flour beetle. , 2008, Insect biochemistry and molecular biology.

[7]  L. Avery,et al.  Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[8]  T. Singer,et al.  The animal and human neuroendocrinology of social cognition, motivation and behavior , 2012, Nature Neuroscience.

[9]  Oliver Hobert,et al.  A Toolkit and Robust Pipeline for the Generation of Fosmid-Based Reporter Genes in C. elegans , 2009, PloS one.

[10]  J. Ashby.  References and Notes , 1999 .

[11]  L. Albizu,et al.  Differential Coupling of the Vasopressin V1b Receptor through Compartmentalization within the Plasma Membrane , 2009, Molecular Pharmacology.

[12]  L. Young,et al.  The neurobiology of pair bonding , 2004, Nature Neuroscience.

[13]  A. Kanda,et al.  Octopus, which owns the most advanced brain in invertebrates, has two members of vasopressin/oxytocin superfamily as in vertebrates , 2003, Regulatory Peptides.

[14]  R. Plasterk,et al.  The G-protein gamma subunit gpc-1 of the nematode C.elegans is involved in taste adaptation. , 2002, The EMBO journal.

[15]  Evan L Ardiel,et al.  An elegant mind: learning and memory in Caenorhabditis elegans. , 2010, Learning & memory.

[16]  Cori Bargmann,et al.  The Caenorhabditis elegans odr-2 gene encodes a novel Ly-6-related protein required for olfaction. , 2001, Genetics.

[17]  Suzanne Rademakers,et al.  Antagonistic sensory cues generate gustatory plasticity in Caenorhabditis elegans , 2006, The EMBO journal.

[18]  M. Hanley,et al.  Stepping up the pressure , 1992, Nature.

[19]  Cori Bargmann,et al.  Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans , 1995, Cell.

[20]  David Posada,et al.  ProtTest: selection of best-fit models of protein evolution , 2005, Bioinform..

[21]  S. Whelan,et al.  A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. , 2001, Molecular biology and evolution.

[22]  Cori Bargmann,et al.  Alternative olfactory neuron fates are specified by the LIM homeobox gene lim-4. , 1999, Genes & development.

[23]  G. Reich.  A new peptide of the oxytocin/vasopressin family isolated from nerves of the cephalopod Octopus vulgaris , 1992, Neuroscience Letters.

[24]  V. Du Vigneaud,et al.  The sequence of amino acids in oxytocin, with a proposal for the structure of oxytocin. , 1953, The Journal of biological chemistry.

[25]  O. Hobert,et al.  A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. , 2001, Development.

[26]  S. Rademakers,et al.  Gustatory plasticity in C. elegans involves integration of negative cues and NaCl taste mediated by serotonin, dopamine, and glutamate. , 2008, Learning & memory.

[27]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[28]  F. Hauser,et al.  Cloning and identification of an oxytocin/vasopressin-like receptor and its ligand from insects , 2008, Proceedings of the National Academy of Sciences.

[29]  J. Maetz,et al.  Présence d'une vasotocine dans la neurohypophyse de la grenouille (Rana esculenta L.) , 1960 .

[30]  R. Acher,et al.  Isolement d'une nouvelle hormone neurohypophysaire, l'isotocine, présente chez les poissons osseux , 1962 .

[31]  H. Satake,et al.  Characterization of a novel vasopressin/oxytocin superfamily peptide and its receptor from an ascidian, Ciona intestinalis , 2008, Peptides.

[32]  A. Hikosaka,et al.  Unique form and osmoregulatory function of a neurohypophysial hormone in a urochordate. , 2008, Endocrinology.

[33]  A. Smit,et al.  A novel G protein-coupled receptor mediating both vasopressin- and oxytocin-like functions of Lys-conopressin in Lymnaea stagnalis , 1995, Neuron.

[34]  Peter Kirsch,et al.  Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine , 2011, Nature Reviews Neuroscience.

[35]  D. Pfaff,et al.  Behavioral effects of progesterone associated with rapid modulation of oxytocin receptors. , 1990, Science.

[36]  R. Acher,et al.  Marsupial neurohypophysial hormones: identification of mesotocin, lysine vasopressin, and phenypressin in the quokka wallaby (Setonix brachyurus). , 1983, General and comparative endocrinology.

[37]  R. Acher,et al.  Structure, processing and evolution of the neurohypophysial hormone-neurophysin precursors. , 1988, Biochimie.

[38]  D. Wied,et al.  Central Nervous System Effects of the Neurohypophyseal Hormones and Related Peptides , 1993, Frontiers in Neuroendocrinology.

[39]  L. Schoofs,et al.  Coevolution of neuropeptidergic signaling systems: from worm to man , 2010, Annals of the New York Academy of Sciences.

[40]  A. van Dorsselaer,et al.  Isolation, structural characterization and biological function of a lysine-conopressin in the central nervous system of the pharyngobdellid leech Erpobdella octoculata. , 1993, European journal of biochemistry.

[41]  S. Husson,et al.  Discovering neuropeptides in Caenorhabditis elegans by two dimensional liquid chromatography and mass spectrometry. , 2005, Biochemical and biophysical research communications.

[42]  M. Elphick,et al.  NGFFFamide and echinotocin: structurally unrelated myoactive neuropeptides derived from neurophysin-containing precursors in sea urchins , 2009, Journal of Experimental Biology.

[43]  O. Gascuel,et al.  A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. , 2003, Systematic biology.

[44]  H. Minakata,et al.  Annetocin, an annelid oxytocin-related peptide, induces egg-laying behavior in the earthworm, Eisenia foetida. , 1996, The Journal of experimental zoology.

[45]  John P. Huelsenbeck,et al.  MRBAYES: Bayesian inference of phylogenetic trees , 2001, Bioinform..

[46]  G. Ruvkun,et al.  Lineage-specific regulators couple cell lineage asymmetry to the transcription of the Caenorhabditis elegans POU gene unc-86 during neurogenesis. , 1996, Genes & development.

[47]  Cori Bargmann,et al.  Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans , 1991, Neuron.

[48]  M. Soloff,et al.  Oxytocin receptors: triggers for parturition and lactation? , 1979, Science.

[49]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[50]  S. R. Wicks,et al.  CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia structure and function in Caenorhabditis elegans. , 2000, Developmental biology.

[51]  J. Culotti,et al.  Osmotic avoidance defective mutants of the nematode Caenorhabditis elegans. , 1978, Genetics.

[52]  H. Akaike.  A new look at the statistical model identification , 1974 .

[53]  Rubén Sánchez,et al.  Phylemon 2.0: a suite of web-tools for molecular evolution, phylogenetics, phylogenomics and hypotheses testing , 2011, Nucleic Acids Res..

[54]  R. Acher,et al.  Phenypressin (Phe2-Arg8-vasopressin), a new neurohypophysial peptide found in marsupials , 1980, Nature.

[55]  G. Ruvkun,et al.  Control of Neural Development and Function in a Thermoregulatory Network by the Lim Homeobox Gene Lin-11 , 2022 .

[56]  J Hoflack,et al.  The Binding Site of Neuropeptide Vasopressin V1a Receptor , 1995, The Journal of Biological Chemistry.

[57]  R. Plasterk,et al.  The G‐protein γ subunit gpc‐1 of the nematode C.elegans is involved in taste adaptation , 2002 .

[58]  V. Ambros,et al.  Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. , 1991, The EMBO journal.

[59]  Korbinian Strimmer,et al.  PAL: an object-oriented programming library for molecular evolution and phylogenetics , 2001, Bioinform..

[60]  D. Bichet,et al.  Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus , 1992, Nature.

[61]  Cori Bargmann,et al.  OSM-9, A Novel Protein with Structural Similarity to Channels, Is Required for Olfaction, Mechanosensation, and Olfactory Adaptation inCaenorhabditis elegans , 1997, The Journal of Neuroscience.