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A diacylglycerol kinase modulates long-term thermotactic behavioral plasticity in C. elegans

Nature Neuroscience volume 9, pages 1499–1505 (2006)Cite this article

Abstract

A memory of prior thermal experience governs Caenorhabditis elegans thermotactic behavior. On a spatial thermal gradient, C. elegans tracks isotherms near a remembered temperature we call the thermotactic set-point (TS). The TS corresponds to the previous cultivation temperature and can be reset by sustained exposure to a new temperature. The mechanisms underlying this behavioral plasticity are unknown, partly because sensory and experience-dependent components of thermotactic behavior have been difficult to separate. Using newly developed quantitative behavioral analyses, we demonstrate that the TS represents a weighted average of a worm's temperature history. We identify the DGK-3 diacylglycerol kinase as a thermal memory molecule that regulates the rate of TS resetting by modulating the temperature range of synaptic output, but not temperature sensitivity, of the AFD thermosensory neurons. These results provide the first mechanistic insight into the basis of experience-dependent plasticity in this complex behavior.

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Figure 1: C. elegans track isotherms around a thermotactic set point (TS) corresponding to their cultivation temperature.
Figure 2: The TS represents an average of a worm's temperature history, and TS resetting does not depend on the presence of bacterial food.
Figure 3: dgk-3 mutants show altered rates of TS resetting.
Figure 4: Mutations in dgk-3 alter the operating range of the AFD neurons upon sustained exposure to new temperatures.

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References

  1. Castellucci, V.F., Carew, T.J. & Kandel, E.R. Cellular analysis of long-term habituation of the gill-withdrawal reflex of Aplysia californica. Science 202, 1306–1308 (1976).

    Article  Google Scholar 

  2. Castellucci, V., Pinsker, H., Kupfermann, I. & Kandel, E.R. Neuronal mechanisms of habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science 167, 1745–1748 (1970).

    Article  CAS  Google Scholar 

  3. Castellucci, V.F. & Kandel, E.R. A quantal analysis of the synaptic depression underlying habituation of the gill-withdrawal reflex in Aplysia. Proc. Natl. Acad. Sci. USA 71, 5004–5008 (1974).

    Article  CAS  Google Scholar 

  4. Bailey, C.H. & Chen, M. Morphological basis of short-term habituation in Aplysia. J. Neurosci. 8, 2452–2459 (1988).

    Article  CAS  Google Scholar 

  5. Bailey, C.H. & Chen, M. Morphological basis of long-term habituation and sensitization in Aplysia. Science 220, 91–93 (1983).

    Article  CAS  Google Scholar 

  6. Bliss, T.V. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. (Lond.) 232, 331–356 (1973).

    Article  CAS  Google Scholar 

  7. Dudek, S.M. & Bear, M.F. Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade. Proc. Natl. Acad. Sci. USA 89, 4363–4367 (1992).

    Article  CAS  Google Scholar 

  8. Yu, D., Ponomarev, A. & Davis, R.L. Altered representation of the spatial code for odors after olfactory classical conditioning; memory trace formation by synaptic recruitment. Neuron 42, 437–449 (2004).

    Article  CAS  Google Scholar 

  9. de Bono, M. & Maricq, A.V. Neuronal substrates of complex behaviors in C. elegans. Annu. Rev. Neurosci. 28, 451–501 (2005).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Goodman, M.B., Hall, D.H., Avery, L. & Lockery, S.R. Active currents regulate sensitivity and dynamic range in C. elegans neurons. Neuron 20, 763–772 (1998).

    Article  CAS  Google Scholar 

  12. Kerr, R. et al. Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans. Neuron 26, 583–594 (2000).

    Article  CAS  Google Scholar 

  13. Hilliard, M.A. et al. In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents. EMBO J. 24, 63–72 (2005).

    Article  CAS  Google Scholar 

  14. Feng, Z., Cronin, C.J., Wittig, J.H., Jr., Sternberg, P.W. & Schafer, W.R. An imaging system for standardized quantitative analysis of C. elegans behavior. BMC Bioinformatics [online] 5, 115 (2004) (doi:10.1186/1471-2105-5-115).

    Article  Google Scholar 

  15. Chung, S.H., Clark, D.A., Gabel, C.V., Mazur, E. & Samuel, A.D. The role of the AFD neuron in C. elegans thermotaxis analyzed using femtosecond laser ablation. BMC Neurosci. [online] 7, 30 (2006) (doi:10.1186/1471-2202-7-30).

    Article  CAS  Google Scholar 

  16. Faumont, S. & Lockery, S.R. The awake behaving worm: simultaneous imaging of neuronal activity and behavior in intact animals at millimeter scale. J. Neurophysiol. 95, 1976–1981 (2006).

    Article  Google Scholar 

  17. Hedgecock, E.M. & Russell, R.L. Normal and mutant thermotaxis in the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 72, 4061–4065 (1975).

    Article  CAS  Google Scholar 

  18. Hutchison, V.H. & Maness, J.D. The role of behavior in temperature acclimation and tolerance in ectotherms. Integ. Compar. Biol. 19, 367–384 (1979).

    Google Scholar 

  19. Satterlee, J.S. et al. Specification of thermosensory neuron fate in C. elegans requires ttx-1, a homolog of otd/Otx. Neuron 31, 943–956 (2001).

    Article  CAS  Google Scholar 

  20. Mori, I. & Ohshima, Y. Neural regulation of thermotaxis in Caenorhabditis elegans. Nature 376, 344–348 (1995).

    Article  CAS  Google Scholar 

  21. Kimura, K.D., Miyawaki, A., Matsumoto, K. & Mori, I. The C. elegans thermosensory neuron AFD responds to warming. Curr. Biol. 14, 1291–1295 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  23. Samuel, A.D., Silva, R.A. & Murthy, V.N. Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic memory. J. Neurosci. 23, 373–376 (2003).

    Article  CAS  Google Scholar 

  24. Ryu, W.S. & Samuel, A.D. Thermotaxis in Caenorhabditis elegans analyzed by measuring responses to defined thermal stimuli. J. Neurosci. 22, 5727–5733 (2002).

    Article  CAS  Google Scholar 

  25. Murakami, H., Bessinger, K., Hellmann, J. & Murakami, S. Aging-dependent and -independent modulation of associative learning behavior by insulin/insulin-like growth factor-1 signal in Caenorhabditis elegans. J. Neurosci. 25, 10894–10904 (2005).

    Article  CAS  Google Scholar 

  26. Mohri, A. et al. Genetic control of temperature preference in the nematode Caenorhabditis elegans. Genetics 169, 1437–1450 (2005).

    Article  CAS  Google Scholar 

  27. Colosimo, M.E. et al. Identification of thermosensory and olfactory neuron-specific genes via expression profiling of single neuron types. Curr. Biol. 14, 2245–2251 (2004).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Sakane, F., Imai, S., Yamada, K. & Kanoh, H. The regulatory role of EF-hand motifs of pig 80K diacylglycerol kinase as assessed using truncation and deletion mutants. Biochem. Biophys. Res. Commun. 181, 1015–1021 (1991).

    Article  CAS  Google Scholar 

  30. Yamada, K., Sakane, F., Matsushima, N. & Kanoh, H. EF-hand motifs of α, β and γ isoforms of diacylglycerol kinase bind calcium with different affinities and conformational changes. Biochem. J. 321, 59–64 (1997).

    Article  CAS  Google Scholar 

  31. Sakane, F., Yamada, K., Imai, S. & Kanoh, H. Porcine 80-kDa diacylglycerol kinase is a calcium-binding and calcium/phospholipid-dependent enzyme and undergoes calcium-dependent translocation. J. Biol. Chem. 266, 7096–7100 (1991).

    CAS  PubMed  Google Scholar 

  32. Sanjuan, M.A., Jones, D.R., Izquierdo, M. & Merida, I. Role of diacylglycerol kinase α in the attenuation of receptor signaling. J. Cell Biol. 153, 207–220 (2001).

    Article  CAS  Google Scholar 

  33. Sakane, F., Kai, M., Wada, I., Imai, S. & Kanoh, H. The C-terminal part of diacylglycerol kinase α lacking zinc fingers serves as a catalytic domain. Biochem. J. 318, 583–590 (1996).

    Article  CAS  Google Scholar 

  34. van Blitterswijk, W.J. & Houssa, B. Properties and functions of diacylglycerol kinases. Cell. Signal. 12, 595–605 (2000).

    Article  CAS  Google Scholar 

  35. Miyawaki, A. et al. Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388, 882–887 (1997).

    Article  CAS  Google Scholar 

  36. Coburn, C. & Bargmann, C.I. A putative cyclic nucleotide-gated channel is required for sensory development and function in C. elegans. Neuron 17, 695–706 (1996).

    Article  CAS  Google Scholar 

  37. Komatsu, H., Mori, I. & Ohshima, Y. Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans. Neuron 17, 707–718 (1996).

    Article  CAS  Google Scholar 

  38. Hofmann, T. et al. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397, 259–263 (1999).

    Article  CAS  Google Scholar 

  39. Nishizuka, Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein C. Science 258, 607–614 (1992).

    Article  CAS  Google Scholar 

  40. Estacion, M., Sinkins, W.G. & Schilling, W.P. Regulation of Drosophila transient receptor potential-like (TrpL) channels by phospholipase C-dependent mechanisms. J. Physiol. (Lond.) 530, 1–19 (2001).

    Article  CAS  Google Scholar 

  41. Maruyama, H., Rakow, T.L. & Maruyama, I.N. Synaptic exocytosis and nervous system development impaired in Caenorhabditis elegans unc-13 mutants. Neuroscience 104, 287–297 (2001).

    Article  CAS  Google Scholar 

  42. Richmond, J.E., Davis, W.S. & Jorgensen, E.M. UNC-13 is required for synaptic vesicle fusion in C. elegans. Nat. Neurosci. 2, 959–964 (1999).

    Article  CAS  Google Scholar 

  43. Raghu, P. et al. Constitutive activity of the light-sensitive channels TRP and TRPL in the Drosophila diacylglycerol kinase mutant, rdgA. Neuron 26, 169–179 (2000).

    Article  CAS  Google Scholar 

  44. Hazel, J.R. & Williams, E.E. The role of alterations in membrane lipid composition in enabling physiological adaptation of organisms to their physical environment. Prog. Lipid Res. 29, 167–227 (1990).

    Article  CAS  Google Scholar 

  45. Cossins, A.R. Homeoviscous adaptation of biological membranes and its functional significance. In Temperature Adaptation of Biological Membranes (ed. Cossins, A.R.) 63–76 (Portland, London, 1994).

    Google Scholar 

  46. Okochi, Y., Kimura, K.D., Ohta, A. & Mori, I. Diverse regulation of sensory signaling by C. elegans nPKC-epsilon/eta TTX-4. EMBO J. 24, 2127–2137 (2005).

    Article  CAS  Google Scholar 

  47. Nurrish, S., Segalat, L. & Kaplan, J.M. Serotonin inhibition of synaptic transmission: GαO decreases the abundance of UNC-13 at release sites. Neuron 24, 231–242 (1999).

    Article  CAS  Google Scholar 

  48. Inada, H. et al. Identification of guanylyl cyclases that function in thermosensory neurons of Caenorhabditis elegans. Genetics 172, 2239–2252 (2006).

    Article  CAS  Google Scholar 

  49. Kuhara, A., Inada, H., Katsura, I. & Mori, I. Negative regulation and gain control of sensory neurons by the C. elegans calcineurin TAX-6. Neuron 33, 751–763 (2002).

    Article  CAS  Google Scholar 

  50. Gomez, M. et al. Ca2+ signaling via the neuronal calcium sensor-1 regulates associative learning and memory in C. elegans. Neuron 30, 241–248 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

We are very grateful to C. Gauthier for technical assistance, the Caenorhabditis Genetics Center for strains, the C. elegans Gene Knockout Consortium for the dgk-3(gk110) allele, I. Mori (Nagoya University) for the nhr-38::YC2.12–expressing transgenic strain, H. Suzuki (University of California, San Diego) for the YC2.12 clone, A. Fire (Stanford University) for the C. elegans expression vectors, and C. Bargmann, L. Griffith, O. Hobert, M. Rosbash and the Sengupta and Samuel labs for discussion and comments on the manuscript. This work was supported by a Human Frontier Science Program cross-disciplinary fellowship (D.B.), the US National Institutes of Health (NS44232, P.S.), and the US National Science Foundation, the McKnight Foundation and the Sloan Foundation (A.D.T.S.).

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  1. Adam Brown

    Present address: Broad Institute, 320 Charles Street, Cambridge, Massachusetts, 02141, USA

Authors and Affiliations

  1. Department of Physics, Harvard University, 17 Oxford Street, Cambridge, 02138, Massachusetts, USA

    David Biron, Christopher Gabel, Damon A Clark & Aravinthan D T Samuel

  2. Department of Biology and National Center for Behavioral Genomics, 415 South Street

    David Biron, Mayumi Shibuya, Sara M Wasserman, Adam Brown & Piali Sengupta

  3. Brandeis University, Waltham, 02454, Massachusetts, USA

    David Biron, Mayumi Shibuya, Sara M Wasserman, Adam Brown & Piali Sengupta

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Contributions

D.B. conducted the behavioral and imaging experiments. M.S., S.M.W., A.B. and P.S. conducted the molecular biology and genetic experiments. C.G. and D.A.C. developed the behavioral and imaging assays. A.B. and C.G. initially noted the dgk-3 mutant phenotype. D.B., A.D.T.S. and P.S. contributed to data analysis and manuscript preparation.

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Correspondence to Piali Sengupta or Aravinthan D T Samuel.

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Supplementary information

Supplementary Fig. 1

Structure of DGK-3. (PDF 125 kb)

Supplementary Video 1

Isothermal tracking exhibited by wild-type animals cultivated at 20 °C and placed on a spatial thermal gradient, ranging from 18 °C on the left to 22 °C on the right. Animals track isotherms around 20 °C. Movie speed ×30. (MOV 264 kb)

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Biron, D., Shibuya, M., Gabel, C. et al. A diacylglycerol kinase modulates long-term thermotactic behavioral plasticity in C. elegans. Nat Neurosci 9, 1499–1505 (2006). https://doi.org/10.1038/nn1796

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