Skip to main content

Thank you for visiting 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.

Synaptic tagging and long-term potentiation


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Bliss. T. V. P. & Collingridge, G. L. Nature 361, 31–39 (1993).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Krug, M., Lössner, B. & Ott, T. Brain Res. Bull. 13, 39–42 (1984).

    CAS  Article  Google Scholar 

  3. 3

    Frey, U., Krug, M., Reymann, K. G. & Matthies, H. Brain Res. 452, 57–65 (1988).

    CAS  Article  Google Scholar 

  4. 4

    Fazeli, M. S., Errington, M. L., Dolphin, A. C. & Bliss, T. V. Brain Res. 473, 51–59 (1988).

    CAS  Article  Google Scholar 

  5. 5

    Otani, S., Marshall, C. J., Tate, W. P., Goddard, G. V. & Abraham, W. C. Neuroscience 28, 519–526 (1989).

    CAS  Article  Google Scholar 

  6. 6

    Fazeli, M. S., Corbet, J., Dunn, M. J., Dolphin, A. C. & Bliss, T. V. P. J. Neurosci. 13, 1346–1353 (1993).

    CAS  Article  Google Scholar 

  7. 7

    Nguyen, P. V., Abel, T. & Kandel, E. R. Science 265, 1104–1107 (1994).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Frey, U., Frey, S., Schollmeier, F. & Krug, M. J. Physiol. 490, 703–711 (1996).

    CAS  Article  Google Scholar 

  9. 9

    Link, W. et al. Proc. Nat; Acad. Sci. USA 92, 5734–5738 (1995).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Davis, L., Banker, G. A. & Steward, O. Nature 330, 477–479 (1987).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Kleiman, R., Banker, G. & Steward, O. Neuron 5, 821–830 (1990).

    CAS  Article  Google Scholar 

  12. 12

    Kang, H. & Schuman, E. M. Science 273, 1402–1406 (1996).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Huang, Y. Y. & Kandel, E. R. Learning & Memory 1, 74–82 (1994).

    CAS  Google Scholar 

  14. 14

    Frey, U., Schollmeier, K., Reymann, K. G. & Seidenbecher, T. Neuroscience 67, 799–807 (1995).

    CAS  Article  Google Scholar 

  15. 15

    Steward, O. & Falk, P. M. J. Neurosci. 6, 412–423 (1986).

    CAS  Article  Google Scholar 

  16. 16

    Lovinger, D. M. & Routtenberg, A. J. Physiol. (Lond.) 400, 321–333 (1988).

    CAS  Article  Google Scholar 

  17. 17

    Stäubli, U. & Chun, D. J. Neurosci. 16, 853–860 (1996).

    Article  Google Scholar 

  18. 18

    Hebb, D. O. The Organization of Behaviour (Wiley, New York, 1949).

    Google Scholar 

  19. 19

    Larson, J. & Lynch, G. Science 232, 985–988 (1986).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Diamond, D. M., Dunwiddie, T. V. & Rose, G. M. J. Neurosci. 8, 4079–4088 (1988).

    CAS  Article  Google Scholar 

  21. 21

    Malenka, R. C. Neuron 6, 53–60 (1991).

    CAS  Article  Google Scholar 

  22. 22

    Abraham, W. C. & Bear, M. F. Trends Neurosci. 19, 126–130 (1996).

    CAS  Article  Google Scholar 

  23. 23

    Rawlins, J. N. P. Behav. Brain Sci. 479–528 (1985).

  24. 24

    Squire, L. R. & Davis, H. P. Annu. Rev. Pharmacol. Toxicol. 21, 323–356 (1981).

    CAS  Article  Google Scholar 

  25. 25

    Brown, R. & Kulik, J. Cognition 5, 73–99 (1977).

    Article  Google Scholar 

  26. 26

    Stanton, P. K. & Sarvey, J. M. J. Neurosci. 4, 3080–3088 (1984).

    CAS  Article  Google Scholar 

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Frey, U., Morris, R. Synaptic tagging and long-term potentiation. Nature 385, 533–536 (1997).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links