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Neuropeptide feedback modifies odor-evoked dynamics in Caenorhabditis elegans olfactory neurons

Nature Neuroscience volume 13, pages 615–621 (2010)Cite this article

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Abstract

Many neurons release classical transmitters together with neuropeptide co-transmitters whose functions are incompletely understood. Here we define the relationship between two transmitters in the olfactory system of C. elegans, showing that a neuropeptide-to-neuropeptide feedback loop alters sensory dynamics in primary olfactory neurons. The AWC olfactory neuron is glutamatergic and also expresses the peptide NLP-1. Worms with nlp-1 mutations show increased AWC-dependent behaviors, suggesting that NLP-1 limits the normal response. The receptor for NLP-1 is the G protein-coupled receptor NPR-11, which acts in postsynaptic AIA interneurons. Feedback from AIA interneurons modulates odor-evoked calcium dynamics in AWC olfactory neurons and requires INS-1, a neuropeptide released from AIA. The neuropeptide feedback loop dampens behavioral responses to odors on short and long timescales. Our results point to neuronal dynamics as a site of behavioral regulation and reveal the ability of neuropeptide feedback to remodel sensory networks on multiple timescales.

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Figure 1: AWC releases NLP-1, which acts on NPR-11 in AIA.
Figure 2: Calcium responses in AIA interneurons require AWC glutamate and NLP-1.
Figure 3: Altered AWC calcium responses in nlp-1 and npr-11 mutants.
Figure 4: Worms with mutations in nlp-1 and npr-11 are defective in olfactory adaptation.
Figure 5: ins-1 is a component of the nlp-1-npr-11 pathway.

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References

  1. White, J.G., Southgate, E., Thomson, J.N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Transact. R. Soc. Lond. B 314, 1–340 (1986).

    Article  CAS  Google Scholar 

  2. Chalfie, M. et al. The neural circuit for touch sensitivity in Caenorhabditis elegans. J. Neurosci. 5, 956–964 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bargmann, C.I. Chemosensation in C. elegans. in WormBook (ed. The C. elegans Research Community) doi:10.1895/wormbook.1.123.1, http://www.wormbook.org (2006).

  4. Bargmann, C.I., Hartwieg, E. & Horvitz, H.R. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74, 515–527 (1993).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. 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  PubMed  PubMed Central  Google Scholar 

  7. Pierce-Shimomura, J.T., Morse, T.M. & Lockery, S.R. The fundamental role of pirouettes in Caenorhabditis elegans chemotaxis. J. Neurosci. 19, 9557–9569 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tsunozaki, M., Chalasani, S.H. & Bargmann, C.I. A behavioral switch: cGMP and PKC signaling in olfactory neurons reverses odor preference in C. elegans. Neuron 59, 959–971 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  10. Nathoo, A.N., Moeller, R.A., Westlund, B.A. & Hart, A.C. Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species. Proc. Natl. Acad. Sci. USA 98, 14000–14005 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wenick, A.S. & Hobert, O. Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in C. elegans. Dev. Cell 6, 757–770 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. Etchberger, J.F. et al. The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron. Genes Dev. 21, 1653–1674 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mody, S.M., Ho, M.K., Joshi, S.A. & Wong, Y.H. Incorporation of Galpha(z)-specific sequence at the carboxyl terminus increases the promiscuity of galpha(16) toward G(i)-coupled receptors. Mol. Pharmacol. 57, 13–23 (2000).

    CAS  PubMed  Google Scholar 

  14. Tallini, Y.N. et al. Imaging cellular signals in the heart in vivo: Cardiac expression of the high-signal Ca2+ indicator GCaMP2. Proc. Natl. Acad. Sci. USA 103, 4753–4758 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tian, L. et al. Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat. Methods 6, 875–881 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lockery, S.R. & Goodman, M.B. The quest for action potentials in C. elegans neurons hits a plateau. Nat. Neurosci. 12, 377–378 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Suzuki, H. et al. In vivo imaging of C. elegans mechanosensory neurons demonstrates a specific role for the MEC-4 channel in the process of gentle touch sensation. Neuron 39, 1005–1017 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. O'Hagan, R., Chalfie, M. & Goodman, M.B. The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals. Nat. Neurosci. 8, 43–50 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Clark, D.A., Biron, D., Sengupta, P. & Samuel, A.D. The AFD sensory neurons encode multiple functions underlying thermotactic behavior in Caenorhabditis elegans. J. Neurosci. 26, 7444–7451 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ramot, D., MacInnis, B.L. & Goodman, M.B. Bidirectional temperature-sensing by a single thermosensory neuron in C. elegans. Nat. Neurosci. 11, 908–915 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mellem, J.E., Brockie, P.J., Zheng, Y., Madsen, D.M. & Maricq, A.V. Decoding of polymodal sensory stimuli by postsynaptic glutamate receptors in C. elegans. Neuron 36, 933–944 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Chronis, N., Zimmer, M. & Bargmann, C.I. Microfluidics for in vivo imaging of neuronal and behavioral activity in Caenorhabditis elegans. Nat. Methods 4, 727–731 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Horoszok, L., Raymond, V., Sattelle, D.B. & Wolstenholme, A.J. GLC-3: a novel fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L-glutamate-gated chloride channel subunit from Caenorhabditis elegans. Br. J. Pharmacol. 132, 1247–1254 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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  PubMed  PubMed Central  Google Scholar 

  25. Sieburth, D., Madison, J.M. & Kaplan, J.M. PKC-1 regulates secretion of neuropeptides. Nat. Neurosci. 10, 49–57 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Colbert, H.A. & Bargmann, C.I. Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans. Neuron 14, 803–812 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Colbert, H.A., Smith, T.L. & Bargmann, C.I. OSM-9, a novel protein with structural similarity to channels, is required for olfaction, mechanosensation, and olfactory adaptation in Caenorhabditis elegans. J. Neurosci. 17, 8259–8269 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. L'Etoile, N.D. et al. The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron 36, 1079–1089 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. Palmitessa, A. et al. Caenorhabditis elegans arrestin regulates neural G protein signaling and olfactory adaptation and recovery. J. Biol. Chem. 280, 24649–24662 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Matsuki, M., Kunitomo, H. & Iino, Y. Goalpha regulates olfactory adaptation by antagonizing Gqalpha-DAG signaling in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 103, 1112–1117 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yamada, K., Hirotsu, T., Matsuki, M., Kunitomo, H. & Iino, Y. GPC-1, a G protein gamma-subunit, regulates olfactory adaptation in Caenorhabditis elegans. Genetics 181, 1347–1357 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kaye, J.A., Rose, N.C., Goldsworthy, B., Goga, A. & L'Etoile, N.D. A 3′UTR pumilio-binding element directs translational activation in olfactory sensory neurons. Neuron 61, 57–70 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tomioka, M. et al. The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans. Neuron 51, 613–625 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Marder, E. & Bucher, D. Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs. Annu. Rev. Physiol. 69, 291–316 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Nassel, D.R. & Homberg, U. Neuropeptides in interneurons of the insect brain. Cell Tissue Res. 326, 1–24 (2006).

    Article  PubMed  Google Scholar 

  36. Burnstock, G. Cotransmission. Curr. Opin. Pharmacol. 4, 47–52 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Demb, J.B. Functional circuitry of visual adaptation in the retina. J. Physiol. (Lond.) 586, 4377–4384 (2008).

    Article  CAS  Google Scholar 

  38. Stein, W., DeLong, N.D., Wood, D.E. & Nusbaum, M.P. Divergent co-transmitter actions underlie motor pattern activation by a modulatory projection neuron. Eur. J. Neurosci. 26, 1148–1165 (2007).

    Article  PubMed  Google Scholar 

  39. Pierce, S.B. et al. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev. 15, 672–686 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kodama, E. et al. Insulin-like signaling and the neural circuit for integrative behavior in C. elegans. Genes Dev. 20, 2955–2960 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ivell, R. & Einspanier, A. Relaxin peptides are new global players. Trends Endocrinol. Metab. 13, 343–348 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Macosko, E.Z. et al. A hub-and-spoke circuit drives pheromone attraction and social behaviour in C. elegans. Nature 458, 1171–1175 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wachowiak, M., Wesson, D.W., Pirez, N., Verhagen, J.V. & Carey, R.M. Low-level mechanisms for processing odor information in the behaving animal. Ann. NY Acad. Sci. 1170, 286–292 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Gomez, C. et al. Heterogeneous targeting of centrifugal inputs to the glomerular layer of the main olfactory bulb. J. Chem. Neuroanat. 29, 238–254 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Ignell, R. et al. Presynaptic peptidergic modulation of olfactory receptor neurons in Drosophila. Proc. Natl. Acad. Sci. USA 106, 13070–13075 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Stein, C. et al. Peripheral mechanisms of pain and analgesia. Brain Res. Brain Res. Rev. 60, 90–113 (2009).

    Article  CAS  Google Scholar 

  47. Li, C. & Kim, K. Neuropeptides. in WormBook (ed. The C. elegans Research Community) doi:10.1895/wormbook.1.142.1, http://www.wormbook.org (2008).

  48. Li, C., Nelson, L.S., Kim, K., Nathoo, A. & Hart, A.C. Neuropeptide gene families in the nematode Caenorhabditis elegans. Ann. NY Acad. Sci. 897, 239–252 (1999).

    Article  CAS  PubMed  Google Scholar 

  49. Kindt, K.S. et al. Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans. Neuron 55, 662–676 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the C. elegans knockout consortium and the Caenorhabditis Genetic Center (CGC) for strains, Y.H. Wang for the α16Z chimera, L. Looger for GCaMP2.2b, Y. Iino for discussions about ins-1, and L. Vosshall, G. Lee, E. Feinberg, M. Tsunozaki, J. Gray, J. Garrison, P. McGrath and members of the Bargmann laboratory for critical help, advice and insights. Peptide synthesis was performed by the Proteomics Resource Center of the Rockefeller University. This work was funded by the Mathers Foundation and by the Howard Hughes Medical Institute (C.I.B.). D.R.A. holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA

    Sreekanth H Chalasani, Saul Kato, Dirk R Albrecht, Takao Nakagawa & Cornelia I Bargmann

  2. Department of Neuroscience, Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, New York, USA

    Saul Kato & L F Abbott

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Contributions

S.H.C. conceived, conducted and interpreted experiments and co-wrote the paper; S.K., D.R.A. and L.F.A. performed and interpreted data analysis; T.N. performed HEK expression experiments; C.I.B. conceived and interpreted experiments and co-wrote the paper.

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Correspondence to Cornelia I Bargmann.

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Chalasani, S., Kato, S., Albrecht, D. et al. Neuropeptide feedback modifies odor-evoked dynamics in Caenorhabditis elegans olfactory neurons. Nat Neurosci 13, 615–621 (2010). https://doi.org/10.1038/nn.2526

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