Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans

Nature Neuroscience volume 15, pages 1675–1682 (2012)Cite this article

Subjects

Abstract

Appetitive behaviors require complex decision making that involves the integration of environmental stimuli and physiological needs. C. elegans mate searching is a male-specific exploratory behavior regulated by two competing needs: food and reproductive appetite. We found that the pigment dispersing factor receptor (PDFR-1) modulates the circuit that encodes the male reproductive drive that promotes male exploration following mate deprivation. PDFR-1 and its ligand, PDF-1, stimulated mate searching in the male, but not in the hermaphrodite. pdf-1 was required in the gender-shared interneuron AIM, and the receptor acted in internal and external environment-sensing neurons of the shared nervous system (URY, PQR and PHA) to produce mate-searching behavior. Thus, the pdf-1 and pdfr-1 pathway functions in non–sex-specific neurons to produce a male-specific, goal-oriented exploratory behavior. Our results indicate that secretin neuropeptidergic signaling is involved in regulating motivational internal states.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: PDF-1 neuropeptide signaling stimulates mate searching.
Figure 2: The PDF-1 and PDFR-1 pathway stimulates dispersal following mate deprivation.
Figure 3: Mate sensation and ray activity modulate the effects of PDF-1 signaling.
Figure 4: pdfr-1 is required in sensory neurons URY, PQR and PHA to produce mate-searching behavior.
Figure 5: The interneuron AIM is a source of PDF-1 for mate-searching behavior.

Similar content being viewed by others

References

  1. Pfaff, D.W. The Physiological Mechanisms of Motivation (Springer Verlag, 1982).

  2. Frisch von, O. Animal Migration (Harper Collins, 1969).

  3. Reppert, S.M. A colorful model of the circadian clock. Cell 124, 233–236 (2006).

    Article  CAS  Google Scholar 

  4. Mowrey, W.R. & Portman, D.S. Sex differences in behavioral decision-making and the modulation of shared neural circuits. Biol. Sex Differ. 3, 8 (2012).

    Article  Google Scholar 

  5. Bendesky, A. & Bargmann, C.I. Genetic contributions to behavioural diversity at the gene-environment interface. Nat. Rev. Genet. 12, 809–820 (2011).

    Article  CAS  Google Scholar 

  6. Lipton, J., Kleemann, G., Ghosh, R., Lints, R. & Emmons, S.W. Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple invertebrate. J. Neurosci. 24, 7427–7434 (2004).

    Article  CAS  Google Scholar 

  7. Barrios, A., Nurrish, S. & Emmons, S.W. Sensory regulation of C. elegans male mate-searching behavior. Curr. Biol. 18, 1865–1871 (2008).

    Article  CAS  Google Scholar 

  8. Kleemann, G., Jia, L. & Emmons, S.W. Regulation of Caenorhabditis elegans male mate searching behavior by the nuclear receptor DAF-12. Genetics 180, 2111–2122 (2008).

    Article  Google Scholar 

  9. Janssen, T. et al. Functional characterization of three G protein–coupled receptors for pigment dispersing factors in Caenorhabditis elegans. J. Biol. Chem. 283, 15241–15249 (2008).

    Article  CAS  Google Scholar 

  10. Janssen, T. et al. Discovery and characterization of a conserved pigment dispersing factor–like neuropeptide pathway in Caenorhabditis elegans. J. Neurochem. 111, 228–241 (2009).

    Article  CAS  Google Scholar 

  11. Wicks, S.R., Yeh, R.T., Gish, W.R., Waterston, R.H. & Plasterk, R.H. Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat. Genet. 28, 160–164 (2001).

    Article  CAS  Google Scholar 

  12. Janke, D.L. et al. Interpreting a sequenced genome: toward a cosmid transgenic library of Caenorhabditis elegans. Genome Res. 7, 974–985 (1997).

    Article  CAS  Google Scholar 

  13. Stewart, H.I. et al. Lethal mutations defining 112 complementation groups in a 4.5 Mb sequenced region of Caenorhabditis elegans chromosome III. Mol. Gen. Genet. 260, 280–288 (1998).

    CAS  PubMed  Google Scholar 

  14. Bendesky, A., Tsunozaki, M., Rockman, M.V., Kruglyak, L. & Bargmann, C.I. Catecholamine receptor polymorphisms affect decision-making in C. elegans. Nature 472, 313–318 (2011).

    Article  CAS  Google Scholar 

  15. Milward, K., Busch, K.E., Murphy, R.J., de Bono, M. & Olofsson, B. Neuronal and molecular substrates for optimal foraging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA (2011).

  16. Gloria-Soria, A. & Azevedo, R.B.R. npr-1 regulates foraging and dispersal strategies in Caenorhabditis elegans. Curr. Biol. 18, 1694–1699 (2008).

    Article  CAS  Google Scholar 

  17. Dickson, L. & Finlayson, K. VPAC and PAC receptors: from ligands to function. Pharmacol. Ther. 121, 294–316 (2009).

    Article  CAS  Google Scholar 

  18. Kimura, K.D., Tissenbaum, H.A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946 (1997).

    Article  CAS  Google Scholar 

  19. Ogg, S. et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994–999 (1997).

    Article  CAS  Google Scholar 

  20. You, Y.-J., Kim, J., Raizen, D.M. & Avery, L. Insulin, cGMP and TGF-β signals regulate food intake and quiescence in C. elegans: a model for satiety. Cell Metab. 7, 249–257 (2008).

    Article  CAS  Google Scholar 

  21. Hills, T., Brockie, P.J. & Maricq, A.V. Dopamine and glutamate control area-restricted search behavior in Caenorhabditis elegans. J. Neurosci. 24, 1217–1225 (2004).

    Article  CAS  Google Scholar 

  22. Wakabayashi, T., Kitagawa, I. & Shingai, R. Neurons regulating the duration of forward locomotion in Caenorhabditis elegans. Neurosci. Res. 50, 103–111 (2004).

    Article  Google Scholar 

  23. Gray, J.M., Hill, J.J. & Bargmann, C.I. A circuit for navigation in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 102, 3184–3191 (2005).

    Article  CAS  Google Scholar 

  24. Chalasani, S.H. et al. Dissecting a circuit for olfactory behavior in Caenorhabditis elegans. Nature 450, 63–70 (2007).

    Article  CAS  Google Scholar 

  25. Barr, M.M. & Sternberg, P.W. A polycystic kidney-disease gene homologue required for male mating behavior in C. elegans. Nature 401, 386–389 (1999).

    CAS  PubMed  Google Scholar 

  26. Barr, M.M. et al. The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Curr. Biol. 11, 1341–1346 (2001).

    Article  CAS  Google Scholar 

  27. Flowers, E.B. et al. The Groucho ortholog UNC-37 interacts with the short Groucho-like protein LSY-22 to control developmental decisions in C. elegans. Development 137, 1799–1805 (2010).

    Article  CAS  Google Scholar 

  28. Kage, E. et al. MBR-1, a novel helix-turn-helix transcription factor, is required for pruning excessive neurites in Caenorhabditis elegans. Curr. Biol. 15, 1554–1559 (2005).

    Article  CAS  Google Scholar 

  29. Aurelio, O. Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization. Science 295, 686–690 (2002).

    Article  CAS  Google Scholar 

  30. Bargmann, C. I. Beyond the connectome: how neuromodulators shape neural circuits. Bioessays 34, 458–465 (2012).

    Article  CAS  Google Scholar 

  31. Bermant, G. & Davidson, J. Biological Bases of Sexual Behavior (Harper & Row, 1974).

  32. Portman, D.S. Genetic control of sex differences in C. elegans neurobiology and behavior. Adv. Genet. 59, 1–37 (2007).

    Article  CAS  Google Scholar 

  33. Jarrell, T.A. et al. The connectome of a decision-making neural network. Science 337, 437–444 (2012).

    Article  CAS  Google Scholar 

  34. Fujii, S. & Amrein, H. Ventral lateral and DN1 clock neurons mediate distinct properties of male sex drive rhythm in Drosophila. Proc. Natl. Acad. Sci. USA 107, 10590–10595 (2010).

    Article  CAS  Google Scholar 

  35. Cardoso, J.C., Pinto, V.C., Vieira, F.A., Clark, M.S. & Power, D.M. Evolution of secretin family GPCR members in the metazoa. BMC Evol. Biol. 6, 108 (2006).

    Article  Google Scholar 

  36. Soria, V. et al. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology 35, 1279–1289 (2010).

    Article  CAS  Google Scholar 

  37. Ressler, K.J. et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 470, 492–497 (2011).

    Article  CAS  Google Scholar 

  38. Tursun, B., Patel, T., Kratsios, P. & Hobert, O. Direct conversion of C. elegans germ cells into specific neuron types. Science 331, 304–308 (2011).

    Article  CAS  Google Scholar 

  39. Coates, J.C. & de Bono, M. Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans. Nature 419, 925–929 (2002).

    Article  CAS  Google Scholar 

  40. Morsci, N.S. & Barr, M.M. Kinesin-3 KLP-6 regulates intraflagellar transport in male-specific cilia of Caenorhabditis elegans. Curr. Biol. 21, 1239–1244 (2011).

    Article  CAS  Google Scholar 

  41. Yu, S., Avery, L., Baude, E. & Garbers, D.L. Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. Proc. Natl. Acad. Sci. USA 94, 3384–3387 (1997).

    Article  CAS  Google Scholar 

  42. Maricq, A.V., Peckol, E., Driscoll, M. & Bargmann, C.I. Mechanosensory signaling in C. elegans mediated by the GLR-1 glutamate receptor. Nature 378, 78–81 (1995).

    Article  CAS  Google Scholar 

  43. Lee, R.Y., Sawin, E.R., Chalfie, M., Horvitz, H.R. & Avery, L. EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in Caenorhabditis elegans. J. Neurosci. 19, 159–167 (1999).

    Article  CAS  Google Scholar 

  44. Pujol, N. et al. A reverse genetic analysis of components of the Toll signaling pathway in Caenorhabditis elegans. Curr. Biol. 11, 809–821 (2001).

    Article  CAS  Google Scholar 

  45. Zhang, Y. et al. Identification of genes expressed in C. elegans touch receptor neurons. Nature 418, 331–335 (2002).

    Article  CAS  Google Scholar 

  46. Altun, Z.F., Chen, B., Wang, Z.W. & Hall, D.H. High-resolution map of Caenorhabditis elegans gap junction proteins. Dev. Dyn. 238, 1936–1950 (2009).

    Article  CAS  Google Scholar 

  47. Lickteig, K.M. et al. Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons. J. Neurosci. 21, 2001–2014 (2001).

    Article  CAS  Google Scholar 

  48. Boulin, T., Etchberger, J.F. & Hobert, O. Reporter gene fusions. in WormBook (ed. The C. elegans Research Community) doi:10.1895/wormbook.1.106.1 (2006).

  49. Bargmann, C.I. & Avery, L. Laser killing of cells in Caenorhabditis elegans. Methods Cell Biol. 48, 225–250 (1995).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Maricq (University of Utah), Rongo (Rutgers University) and Hobert (Columbia University) laboratories for strains and reagents, and the Mitani laboratory (Tokyo Women's Medical College) and Japan's National BioResource Project for mutants. Additional strains were obtained from the Caenorhabditis Genetics Center. We thank R. Poole and members of the Barr laboratory for advice and many helpful discussions on the manuscript and L. Vaynerchuk for experimental aid. This research was supported by US National Institutes of Health grant 2R01DK059418 to M.M.B.

Author information

Author notes

  1. Arantza Barrios & Rajarshi Ghosh

    Present address: Present addresses: Department of Cell and Developmental Biology, University College London, London, UK (A.B.), Car Icahn Laboratory, Princeton University, Princeton, New Jersey, USA (R.G.).,

Authors and Affiliations

  1. Department of Genetics, Rutgers University, Piscataway, New Jersey, USA

    Arantza Barrios & Maureen M Barr

  2. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA

    Rajarshi Ghosh, Chunhui Fang & Scott W Emmons

Authors
  1. Arantza Barrios
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajarshi Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chunhui Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Scott W Emmons
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maureen M Barr
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.B. designed and performed the experiments and co-wrote the manuscript. R.G. performed the genetic screen. C.F. contributed to mapping process. S.W.E. and M.M.B. co-wrote and discussed the manuscript with A.B.

Corresponding author

Correspondence to Arantza Barrios.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3 (PDF 1428 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrios, A., Ghosh, R., Fang, C. et al. PDF-1 neuropeptide signaling modulates a neural circuit for mate-searching behavior in C. elegans. Nat Neurosci 15, 1675–1682 (2012). https://doi.org/10.1038/nn.3253

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3253

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing