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:

G(o) signaling is required for Drosophila associative learning

Nature Neuroscience volume 9, pages 1036–1040 (2006)Cite this article

Abstract

Heterotrimeric G(o) is one of the most abundant proteins in the brain, yet relatively little is known of its neural functions in vivo. Here we demonstrate that G(o) signaling is required for the formation of associative memory. In Drosophila melanogaster, pertussis toxin (PTX) is a selective inhibitor of G(o) signaling. The postdevelopmental expression of PTX within mushroom body neurons robustly and reversibly inhibits associative learning. The effect of G(o) inhibition is distributed in both γ- and α/β-lobe mushroom body neurons. However, the expression of PTX in neurons adjacent to the mushroom bodies does not affect memory. PTX expression also does not interact genetically with a rutabaga adenylyl cyclase loss-of-function mutation. Thus, G(o) defines a new signaling pathway required in mushroom body neurons for the formation of associative memory.

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: PTX expression in adult mushroom bodies eliminates 3-min memory.
Figure 2: PTX expression does not kill the mushroom body neurons.
Figure 3: The PTX effect on learning maps to the α/β- and γ-lobe neurons of the mushroom bodies.
Figure 4: G(o) function in olfactory learning and memory is independent of rutabaga.

Similar content being viewed by others

References

  1. Tully, T. & Quinn, W.G. Classical conditioning and retention in normal and mutant Drosophila melanogaster. J. Comp. Physiol. [A] 157, 263–277 (1985).

    Article  CAS  Google Scholar 

  2. Gerber, B., Tanimoto, H. & Heisenberg, M. Evaluating the evidence from fruit flies. Curr. Opin. Neurobiol. 14, 737–744 (2004).

    Article  CAS  Google Scholar 

  3. Dudai, Y., Jan, Y.N., Byers, D., Quinn, W.G. & Benzer, S. dunce, a mutant of Drosophila deficient in learning. Proc. Natl. Acad. Sci. USA 73, 1684–1689 (1976).

    Article  CAS  Google Scholar 

  4. Byers, D., Davis, R.L. & Kiger, J.A. Jr. Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster. Nature 289, 79–81 (1981).

    Article  CAS  Google Scholar 

  5. Skoulakis, E.M., Kalderon, D. & Davis, R.L. Preferential expression of the catalytic subunit of PKA in the mushroom bodies and its role in learning and memory. Neuron 11, 197–208 (1993).

    Article  CAS  Google Scholar 

  6. Goodwin, S.F. et al. Defective learning in mutants of the Drosophila gene for a regulatory subunit of cAMP-dependent protein kinase. J. Neurosci. 17, 8817–8827 (1997).

    Article  CAS  Google Scholar 

  7. Connolly, J.B. et al. Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies. Science 274, 2104–2107 (1996).

    Article  CAS  Google Scholar 

  8. Zars, T., Fischer, M., Schulz, R. & Heisenberg, M. Localization of a short-term memory in Drosophila. Science 288, 672–675 (2000).

    Article  CAS  Google Scholar 

  9. McGuire, S.E., Le, P.T., Osborn, A.J., Matsumoto, K. & Davis, R.L. Spatiotemporal rescue of memory dysfunction in Drosophila. Science 302, 1765–1768 (2003).

    Article  CAS  Google Scholar 

  10. Mao, Z., Roman, G., Zong, L. & Davis, R.L. Pharmacogenetic rescue in time and space of the rutabaga memory impairment by using Gene-Switch. Proc. Natl. Acad. Sci. USA 101, 198–203 (2004).

    Article  CAS  Google Scholar 

  11. Sternweis, P.C. & Robishaw, J.D. Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J. Biol. Chem. 259, 13806–13813 (1984).

    CAS  PubMed  Google Scholar 

  12. Jiang, M. et al. Multiple neurological abnormalities in mice deficient in the G protein Go . Proc. Natl. Acad. Sci. USA 95, 3269–3274 (1998).

    Article  CAS  Google Scholar 

  13. Mendel, J.E. et al. Participation of the protein Go in multiple aspects of behavior in C. elegans. Science 267, 1652–1655 (1995).

    Article  CAS  Google Scholar 

  14. Frémion, F. et al. The heterotrimeric protein Go is required for the formation of heart epithelium in Drosophila. J. Cell Biol. 145, 1063–1076 (1999).

    Article  Google Scholar 

  15. Thambi, N.C., Quan, F., Wolfgang, W.J., Spiegel, A. & Forte, M. Immunological and molecular characterization of Go alpha-like proteins in the Drosophila central nervous system. J. Biol. Chem. 264, 18552–18560 (1989).

    CAS  PubMed  Google Scholar 

  16. Guillen, A. et al. A Go-like protein in Drosophila melanogaster and its expression in memory mutants. EMBO J. 9, 1449–1455 (1990).

    Article  CAS  Google Scholar 

  17. Katada, T., Tamura, M. & Ui, M. The A protomer of islet-activating protein, pertussis toxin, as an active peptide catalyzing ADP-ribosylation of a membrane protein. Arch. Biochem. Biophys. 224, 290–298 (1983).

    Article  CAS  Google Scholar 

  18. Hopkins, R.S., Stamnes, M.A., Simon, M.I. & Hurley, J.B. Cholera toxin and pertussis toxin substrates and endogenous ADP-ribosyltransferase activity in Drosophila melanogaster. Biochim. Biophys. Acta 970, 355–362 (1988).

    Article  CAS  Google Scholar 

  19. Fitch, C.L. et al. Pertussis toxin expression in Drosophila alters the visual response and blocks eating behaviour. Cell. Signal. 5, 187–207 (1993).

    Article  CAS  Google Scholar 

  20. Osterwalder, T., Yoon, K.S., White, B.H. & Keshishian, H. A conditional tissue-specific transgene expression system using inducible GAL4. Proc. Natl. Acad. Sci. USA 98, 12596–12601 (2001).

    Article  CAS  Google Scholar 

  21. Schwaerzel, M., Heisenberg, M. & Zars, T. Extinction antagonizes olfactory memory at the subcellular level. Neuron 35, 951–960 (2002).

    Article  CAS  Google Scholar 

  22. Crittenden, J.R., Skoulakis, E.M., Han, K.A., Kalderon, D. & Davis, R.L. Tripartite mushroom body architecture revealed by antigenic markers. Learn. Mem. 5, 38–51 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Waddell, S., Armstrong, J.D., Kitamoto, T., Kaiser, K. & Quinn, W.G. The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory. Cell 103, 805–813 (2000).

    Article  CAS  Google Scholar 

  24. Dubnau, J., Grady, L., Kitamoto, T. & Tully, T. Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory. Nature 411, 476–480 (2001).

    Article  CAS  Google Scholar 

  25. Isabel, G., Pascual, A. & Preat, T. Exclusive consolidated memory phases in Drosophila. Science 304, 1024–1027 (2004).

    Article  CAS  Google Scholar 

  26. Strausfeld, N.J., Sinakevitch, I. & Vilinsky, I. The mushroom bodies of Drosophila melanogaster: an immunocytological and golgi study of Kenyon cell organization in the calyces and lobes. Microsc. Res. Tech. 62, 151–169 (2003).

    Article  Google Scholar 

  27. Taussig, R., Tang, W.J., Hepler, J.R. & Gilman, A.G. Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases. J. Biol. Chem. 269, 6093–6100 (1994).

    CAS  PubMed  Google Scholar 

  28. Sharma, S.K., Klee, W.A. & Nirenberg, M. Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance. Proc. Natl. Acad. Sci. USA 72, 3092–3096 (1975).

    Article  CAS  Google Scholar 

  29. Ikeda, S.R. Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits. Nature 380, 255–258 (1996).

    Article  CAS  Google Scholar 

  30. Roman, G., He, J. & Davis, R.L. A new series of Drosophila expression vectors suitable for behavioral rescue. Biotechniques 27, 54–56 (1999).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors wish to thank J. Maynard (Stanford University, Palo Alto, California) for providing the 1B7 monoclonal antibody to PTX, and R. Davis, K. Choi and M. Mancini for sharing space in their laboratories. This work was supported by NS042185-04 awarded to G.R.

Author information

Author notes

  1. Gregg Roman

    Present address: Department of Biology and Biochemistry, University of Houston, Houston, Texas, 77204, USA

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, Texas, USA

    Jacob Ferris, Hong Ge, Lingzhi Liu & Gregg Roman

Authors
  1. Jacob Ferris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lingzhi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregg Roman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The behavioral experiments were performed by both J.F. and H.G. H.G. performed the immunohistochemistry and L.L. performed the western blot analysis. G.R. generated the PTX transgene and the tested genotypes.

Corresponding author

Correspondence to Gregg Roman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Lethality of P{UASPTX} Expression. (PDF 50 kb)

Supplementary Table 2

Naïve odour and shock avoidance in a 2-minute T-Maze assay. (PDF 78 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ferris, J., Ge, H., Liu, L. et al. G(o) signaling is required for Drosophila associative learning. Nat Neurosci 9, 1036–1040 (2006). https://doi.org/10.1038/nn1738

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn1738

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