Synaptic tagging and long-term potentiation (original) (raw)

Nature volume 385, pages 533–536 (1997)Cite this article

Abstract

Repeated stimulation of hippocampal neurons can induce an immediate and prolonged increase in synaptic strength that is called long-term potentiation (LTP)—the primary cellular model of memory in the mammalian brain1. An early phase of LTP (lasting less than three hours) can be dissociated from late-phase LTP by using inhibitors of transcription and translation2–8. Because protein synthesis occurs mainly in the cell body9–12, whereas LTP is input-specific, the question arises of how the synapse specificity of late LTP is achieved without elaborate intracellular protein trafficking. We propose that LTP initiates the creation of a short-lasting protein-synthesis-independent 'synaptic tag' at the potentiated synapse which sequesters the relevant protein(s) to establish late LTP. In support of this idea, we now show that weak tetanic stimulation, which ordinarily leads only to early LTP, or repeated tetanization in the presence of protein-synthesis inhibitors, each results in protein-synthesis-dependent late LTP, provided repeated tetanization has already been applied at another input to the same population of neurons. The synaptic tag decays in less than three hours. These findings indicate that the persistence of LTP depends not only on local events during its induction, but also on the prior activity of the neuron.

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References

  1. Bliss. T. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).
    Article ADS CAS Google Scholar
  2. Krug, M., Lössner, B. & Ott, T. Brain Res. Bull. 13, 39–42 (1984).
    Article CAS Google Scholar
  3. Frey, U., Krug, M., Reymann, K. G. & Matthies, H. Brain Res. 452, 57–65 (1988).
    Article CAS Google Scholar
  4. Fazeli, M. S., Errington, M. L., Dolphin, A. C. & Bliss, T. V. Brain Res. 473, 51–59 (1988).
    Article CAS Google Scholar
  5. Otani, S., Marshall, C. J., Tate, W. P., Goddard, G. V. & Abraham, W. C. Neuroscience 28, 519–526 (1989).
    Article CAS Google Scholar
  6. Fazeli, M. S., Corbet, J., Dunn, M. J., Dolphin, A. C. & Bliss, T. V. P. J. Neurosci. 13, 1346–1353 (1993).
    Article CAS Google Scholar
  7. Nguyen, P. V., Abel, T. & Kandel, E. R. Science 265, 1104–1107 (1994).
    Article ADS CAS Google Scholar
  8. Frey, U., Frey, S., Schollmeier, F. & Krug, M. J. Physiol. 490, 703–711 (1996).
    Article CAS Google Scholar
  9. Link, W. et al. Proc. Nat; Acad. Sci. USA 92, 5734–5738 (1995).
    Article ADS CAS Google Scholar
  10. Davis, L., Banker, G. A. & Steward, O. Nature 330, 477–479 (1987).
    Article ADS CAS Google Scholar
  11. Kleiman, R., Banker, G. & Steward, O. Neuron 5, 821–830 (1990).
    Article CAS Google Scholar
  12. Kang, H. & Schuman, E. M. Science 273, 1402–1406 (1996).
    Article ADS CAS Google Scholar
  13. Huang, Y. Y. & Kandel, E. R. Learning & Memory 1, 74–82 (1994).
    CAS Google Scholar
  14. Frey, U., Schollmeier, K., Reymann, K. G. & Seidenbecher, T. Neuroscience 67, 799–807 (1995).
    Article CAS Google Scholar
  15. Steward, O. & Falk, P. M. J. Neurosci. 6, 412–423 (1986).
    Article CAS Google Scholar
  16. Lovinger, D. M. & Routtenberg, A. J. Physiol. (Lond.) 400, 321–333 (1988).
    Article CAS Google Scholar
  17. Stäubli, U. & Chun, D. J. Neurosci. 16, 853–860 (1996).
    Article Google Scholar
  18. Hebb, D. O. The Organization of Behaviour (Wiley, New York, 1949).
    Google Scholar
  19. Larson, J. & Lynch, G. Science 232, 985–988 (1986).
    Article ADS CAS Google Scholar
  20. Diamond, D. M., Dunwiddie, T. V. & Rose, G. M. J. Neurosci. 8, 4079–4088 (1988).
    Article CAS Google Scholar
  21. Malenka, R. C. Neuron 6, 53–60 (1991).
    Article CAS Google Scholar
  22. Abraham, W. C. & Bear, M. F. Trends Neurosci. 19, 126–130 (1996).
    Article CAS Google Scholar
  23. Rawlins, J. N. P. Behav. Brain Sci. 479–528 (1985).
  24. Squire, L. R. & Davis, H. P. Annu. Rev. Pharmacol. Toxicol. 21, 323–356 (1981).
    Article CAS Google Scholar
  25. Brown, R. & Kulik, J. Cognition 5, 73–99 (1977).
    Article Google Scholar
  26. Stanton, P. K. & Sarvey, J. M. J. Neurosci. 4, 3080–3088 (1984).
    Article CAS Google Scholar

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Author notes

  1. Richard G. M. Morris: Centre for Neuroscience, University of Edinburgh, Crichton Street, Edinburgh EH8 9LE, UK

Authors and Affiliations

  1. Federal Institute for Neurobiology, Gene Regulation and Plasticity, PO Box 1860, Brenneckestrasse 6, 39008, Magdeburg, Germany
    Uwe Frey & Richard G. M. Morris

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  1. Uwe Frey
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  2. Richard G. M. Morris
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Frey, U., Morris, R. Synaptic tagging and long-term potentiation.Nature 385, 533–536 (1997). https://doi.org/10.1038/385533a0

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