Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation (original) (raw)

Nature volume 345, pages 718–721 (1990)Cite this article

Abstract

IN both vertebrates and invertebrates, long-term memory differs from short-term in requiring protein synthesis during training1,2. Studies of the gill and siphon withdrawal reflex in Aplysia indicate that similar requirements can be demonstrated at the level of sensory and motor neurons which may participate in memory storage. A single application of serotonin3, a transmitter that mediates sensitization, to individual sensory and motor cells in dissociated cell cultures leads to enhanced transmitter release from the sensory neurons that is independent of new macromolecular synthesis. Five applications of serotonin cause a long-term enhancement, lasting one or more days, which requires translation and transcription2,3. Prolonged application or intracellular injection into the sensory neuron of cyclic AMP, a second messenger for the action of serotonin, also produce long-term increases in synaptic strength4,5, suggesting that some of the gene products important for long-term facilitation are cAMP-inducible. In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA. The cAMP-responsive element (CRE) binds a protein dimer of relative molecular mass 43,000, the CRE-binding protein (CREBP), which has been purified and shown to increase transcription when phosphorylated by the A kinase6–11. Here we show that extracts of the Aplysia central nervous system and extracts of sensory neurons contain a set of proteins, including one with properties similar to mammalian CREBPs, that specifically bind the mammalian CRE sequence. Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation. Taken together, these observations suggest that one or more CREB-like transcriptional activators are required for long-term facilitation.

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

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

References

  1. Davis, H. P. & Squire, L. R. Psychol. Bull. 96, 518–559 (1984).
    Article CAS Google Scholar
  2. Castellucci, V. F., Blumenfeld, H., Goelet, P. & Kandel, E. R. J. Neurobiol. 20, 1–9 (1989).
    Article CAS Google Scholar
  3. Montarolo, P. G. et al. Science 238, 1249–1254 (1986).
    Article ADS Google Scholar
  4. Schacher, S., Castellucci, V. F. & Kandel, E. R. Science 240, 1667–1669 (1988).
    Article ADS CAS Google Scholar
  5. Scholz, K. P. & Byrne, J. H. Science 240, 1664–1666 (1988).
    Article ADS CAS Google Scholar
  6. Montminy, M. R., Sevarino, K. A., Wagner, J. A., Mandel, G. & Goodman, R. H. Proc. natn. Acad. Sci. U.S.A. 83, 6682–6686 (1986).
    Article ADS CAS Google Scholar
  7. Montminy, M. R., & Bilezikjian, L. M. Nature 238, 175–178 (1987).
    Article ADS Google Scholar
  8. Yamamoto, K. K., Gonzalez, G. A., Biggs, W. H. III & Montminy, M. R. Nature 334, 494–498 (1988).
    Article ADS CAS Google Scholar
  9. Comb, M., Hyman, S. E. & Goodman, H. M. Trends Neurosci. 10, 473–478 (1987).
    Article CAS Google Scholar
  10. Comb, M., Birnberg, N. C., Seasholtz, A., Hebert, E. & Goodman, H. M. Nature 323, 353–356 (1986).
    Article ADS CAS Google Scholar
  11. Jones, R. H. & Jones, N. C. Proc. natn. Acad. Sci. U.S.A. 86, 2176–2180 (1989).
    Article ADS CAS Google Scholar
  12. Gonzalez, G. A. et al. Nature 337, 749–752 (1989).
    Article ADS CAS Google Scholar
  13. Fink, J. S. et al. Proc. natn. Acad. Sci. U.S.A. 85, 6662–6666 (1988).
    Article ADS CAS Google Scholar
  14. Deutsch, P. J., Hoeffer, J. P., Jameson, J. L. & Habener, J. F. Proc. natn. Acad. Sci. U.S.A. 85, 7922–7926 (1988).
    Article ADS CAS Google Scholar
  15. Angel, P. et al. Cell 49, 729–739 (1987).
    Article CAS Google Scholar
  16. Hurst, H. C. & Jones, N. C. Genes Dev. 1, 1132–1146 (1987).
    Article CAS Google Scholar
  17. Dale, N., Kandel, E. R. & Schacher, S. Science 239, 282–285 (1988).
    Article ADS CAS Google Scholar
  18. Schacher, S. J. Neurosci. 5, 2028–2034 (1985).
    Article CAS Google Scholar
  19. Wu, C. et al. Science 238, 1247–1253 (1987).
    Article ADS CAS Google Scholar
  20. Sen, R. & Baltimore, D. Cell 46, 705–716 (1986).
    Article CAS Google Scholar
  21. Gilman, M. Z. et al. Cold Spring Harbor Symp. quant. Biol. 53, 761–767 (1988).
    Article CAS Google Scholar
  22. Goelet, P., Castellucci, V. G., Schacher, S. & Kandel, E. R. Nature 322, 419–422 (1986).
    Article ADS CAS Google Scholar
  23. VanBeveren, C., van Straaten, F., Curran, T., Muiller, R. & Verma, I. M. Cell 32, 1241–1255 (1983).
    Article CAS Google Scholar
  24. Matrisian, L. M., Leroy, P., Ruhlmann, C., Gesnel, M. C. & Breathnach, R. Molec. cell. Biol. 6, 1679–1686 (1986).
    Article CAS Google Scholar
  25. Prywes, R. & Roeder, R. G. Cell 47, 777–784 (1986).
    Article CAS Google Scholar
  26. Prywes, R. & Roeder, R. G. Molec. cell. Biol. 7, 3482–3489 (1987).
    Article CAS Google Scholar
  27. Schacher, S. & Proshansky, E. J. Neurosci. 3, 2403–2413 (1983).
    Article CAS Google Scholar

Download references

Author information

Author notes

  1. Binyamin Hochner
    Present address: Institute of Life Sciences, The Otto Loewi Center Neurobiology Unit, The Hebrew University, Jerusalem, Israel

Authors and Affiliations

  1. Howard Hughes Medical Institute and Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, 722 West 168th Street, New York, New York, 10032, USA
    Pramod K. Dash, Binyamin Hochner & Eric R. Kandel

Authors

  1. Pramod K. Dash
    You can also search for this author inPubMed Google Scholar
  2. Binyamin Hochner
    You can also search for this author inPubMed Google Scholar
  3. Eric R. Kandel
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Dash, P., Hochner, B. & Kandel, E. Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation.Nature 345, 718–721 (1990). https://doi.org/10.1038/345718a0

Download citation