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.

Dendritic spine changes associated with hippocampal long-term synaptic plasticity


Long-term enhancement of synaptic efficacy in the hippocampus is an important model for studying the cellular mechanisms of neuronal plasticity, circuit reorganization, and even learning and memory1. Although these long-lasting functional changes are easy to induce, it has been very difficult to demonstrate that they are accompanied or even caused by morphological changes on the subcellular level. Here we combined a local superfusion technique2,3 with two-photon imaging4, which allowed us to scrutinize specific regions of the postsynaptic dendrite where we knew that the synaptic changes had to occur. We show that after induction of long-lasting (but not short-lasting) functional enhancement of synapses in area CA1, new spines appear on the postsynaptic dendrite, whereas in control regions on the same dendrite or in slices where long-term potentiation was blocked, no significant spine growth occurred.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Experimental setup.
Figure 2: New spines emerge after the induction of LTP.
Figure 3: Experiments that produced a change in synaptic efficacy.
Figure 4: Control experiments Three representative experiments with no change in synaptic efficacy.
Figure 5: Quantitative results.


  1. Bliss, T. V. P. & Collingridge, G. L. Asynaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).

    ADS  CAS  Article  Google Scholar 

  2. Veselovsky, N. S., Engert, F. & Lux, H. D. Fast local superfusion technique. Pflügers Arch. 432, 351–354 (1996).

    CAS  Article  Google Scholar 

  3. Engert, F. & Bonhoeffer, T. Synapse specificity of long-term potentiation breaks down at short distances. Nature 388, 279–284 (1997).

    ADS  CAS  Article  Google Scholar 

  4. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73–76 (1990).

    ADS  CAS  Article  Google Scholar 

  5. Woolley, C. S., Gould, E., Frankfurt, M. & McEwen, B. S. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J. Neurosci. 10, 4035–4039 (1990).

    CAS  Article  Google Scholar 

  6. Moser, M.-B., Trommald, M. & Andersen, P. An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses. Proc. Natl Acad. Sci. USA 91, 12673–12675 (1994).

    ADS  CAS  Article  Google Scholar 

  7. Collin, C., Miyaguchi, K. & Segal, M. Dendritic spine density and LTP induction in cultured hippocampal slices. J. Neurophysiol. 77, 1614–1623 (1997).

    CAS  Article  Google Scholar 

  8. McKinney, R. A., Capogna, M., Dürr, R., Gähwiler, B. H. & Thompson, S. M. Miniature synaptic events maintain dendritic spines via AMPA receptor activation. Nature Neurosci. 2, 44–49 (1999).

    CAS  Article  Google Scholar 

  9. Desmond, N. L. & Levy, W. B. Morphological correlates of long-term potentiation imply the modification of existing synapses, not synaptogenesis, in the hippocampal dentate gyrus. Synapse 5, 139–143 (1990).

    CAS  Article  Google Scholar 

  10. Hosokawa, T., Rusakov, D. A., Bliss, T. V. & Fine, A. Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: Evidence for changes in length and orientation associated with chemically induced LTP. J. Neurosci. 15, 5560–5573 (1995).

    CAS  Article  Google Scholar 

  11. Buchs, P. A. & Muller, D. Induction of long-term potentiation is associated with major ultrastructural changes of activated synapses. Proc. Natl Acad. Sci. USA 93, 8040–8045 (1996).

    ADS  CAS  Article  Google Scholar 

  12. Sorra, K. E. & Harris, K. M. Stability in synapse number and size at 2 hr after long-term potentiation in hippocampal area CA1. J. Neurosci. 18, 658–671 (1998).

    CAS  Article  Google Scholar 

  13. Crick, F. Do dendritic spines twitch? Trends Neurosci. 5, 44–46 (1982).

    Article  Google Scholar 

  14. Svoboda, K., Tank, D. W. & Denk, W. Direct measurement of coupling between dendritic spines and shafts. Science 272, 716–719 (1996).

    ADS  CAS  Article  Google Scholar 

  15. Fischer, M., Kaech, S., Knutti, D. & Matus, A. Rapid actin-based plasticity in dendritic spines. Neuron 20, 847–854 (1998).

    CAS  Article  Google Scholar 

  16. Dunaevsky, A., Heintz, N., Mason, C. A. & Yuste, R. Two-photon imaging of dendritic spines of cerebellar and cortical cells transfected with GFP. Soc. Neurosci. Abstr. 24, 316.1 (1998).

    Google Scholar 

  17. Gray, E. G. Electron microscopy of synaptic contacts on dendritic spines of the cerebral cortex. Nature 183, 1592–1593 (1959).

    ADS  CAS  Article  Google Scholar 

  18. Bolshakov, V. Y., Golan, H., Kandel, E. R. & Siegelbaum, S. A. Recruitment of new sites of synaptic transmission during the cAMP-dependent late phase of LTP at CA3–CA1 synapses in the hippocampus. Neuron 19, 635–651 (1997).

    CAS  Article  Google Scholar 

  19. Bienenstock, E. L., Cooper, L. N. & Munro, P. W. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32–48 (1982).

    CAS  Article  Google Scholar 

  20. Miller, K. D. & MacKay, D. C. The role of constraints in Hebbian learning. Neural Comput. 6, 100–126 (1994).

    Article  Google Scholar 

  21. Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C. & Nelson, S. B. Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391, 892–896 (1998).

    ADS  CAS  Article  Google Scholar 

  22. Gähwiler, B. H. Organotypic monolayer cultures of nervous tissue. J. Neurosci. Meth. 4, 329–342 (1981).

    Article  Google Scholar 

  23. Bonhoeffer, T., Staiger, V. & Aertsen, A. Synaptic plasticity in rat hippocampal slice cultures: Local ‘Hebbian’ conjunction of pre- and postsynaptic stimulation leads to distributed synaptic enhancement. Proc. Natl Acad. Sci. USA 86, 8113–8117 (1989).

    ADS  CAS  Article  Google Scholar 

Download references


We thank I. Kehrer for help with the evaluation of the data, and M. Hübener, M.Korte and M. Meister for comments on the manuscript.

Author information

Authors and Affiliations


Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Engert, F., Bonhoeffer, T. Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66–70 (1999).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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

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