Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex


Do new synapses form in the adult cortex to support experience-dependent plasticity? To address this question, we repeatedly imaged individual pyramidal neurons in the mouse barrel cortex over periods of weeks. We found that, although dendritic structure is stable, some spines appear and disappear. Spine lifetimes vary greatly: stable spines, about 50% of the population, persist for at least a month, whereas the remainder are present for a few days or less. Serial-section electron microscopy of imaged dendritic segments revealed retrospectively that spine sprouting and retraction are associated with synapse formation and elimination. Experience-dependent plasticity of cortical receptive fields was accompanied by increased synapse turnover. Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Chronic time-lapse imaging of dendritic spines in the barrel cortex in vivo.
Figure 2: Dendritic branches are stable over weeks.
Figure 3: New spines establish synapses.
Figure 4: In vivo imaging of putative synapse formation and elimination.
Figure 5: Spines appear and disappear with broadly distributed lifetimes, without changing spine density.
Figure 6: Altering sensory experience increases spine turnover rates.
Figure 7: Experience-dependent receptive field plasticity.


  1. 1

    Squire, L. R. & Alvarez, P. Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr. Opin. Neurobiol. 5, 169–177 (1995)

    CAS  Article  Google Scholar 

  2. 2

    Jenkins, W. M., Merzenich, M. M., Ochs, M. T., Allard, T. & Guic-Robles, E. Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation. J. Neurophysiol. 63, 82–104 (1990)

    CAS  Article  Google Scholar 

  3. 3

    Bakin, J. S. & Weinberger, N. M. Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig. Brain. Res. 536, 271–286 (1990)

    CAS  Article  Google Scholar 

  4. 4

    Gilbert, C. D. & Wiesel, T. N. Receptive field dynamics in adult primary visual cortex. Nature 356, 150–152 (1992)

    ADS  CAS  Article  Google Scholar 

  5. 5

    Diamond, M. E., Huang, W. & Ebner, F. F. Laminar comparison of somatosensory cortical plasticity. Science 265, 1885–1888 (1994)

    ADS  CAS  Article  Google Scholar 

  6. 6

    Florence, S. L., Taub, H. B. & Kaas, J. H. Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. Science 282, 1117–1121 (1998)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Wang, X., Merzenich, M. M., Sameshima, K. & Jenkins, W. M. Remodelling of hand representation in adult cortex determined by timing of tactile stimulation. Nature 378, 71–75 (1995)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Tanzi, E. I fatti i le induzione nell'odierna istologia del sistema nervoso. Riv. Sper. Freniatr. 19, 419–472 (1893)

    Google Scholar 

  9. 9

    Martin, S. J., Grimwood, P. D. & Morris, R. G. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000)

    CAS  Article  Google Scholar 

  10. 10

    Ramon y Cajal, S. Neue Darstellung vom histologischen Bau des Centralnervensystems. Arch. Anat. Physiol. Anat. Abt. Suppl., 319–428 (1893)

  11. 11

    Darian-Smith, C. & Gilbert, C. D. Axonal sprouting accompanies functional reorganization in adult cat striate cortex. Nature 368, 737–740 (1994)

    ADS  CAS  Article  Google Scholar 

  12. 12

    Volkmar, F. R. & Greenough, W. T. Differential rearing effects on rat visual cortical plasticity. Science 176, 1445–1447 (1972)

    ADS  CAS  Article  Google Scholar 

  13. 13

    Ziv, N. E. & Smith, S. J. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17, 91–102 (1996)

    CAS  Article  Google Scholar 

  14. 14

    Stepanyants, A., Hof, P. R. & Chklovskii, D. B. Geometry and structural plasticity of synaptic connectivity. Neuron 34, 275–288 (2002)

    CAS  Article  Google Scholar 

  15. 15

    Knott, G. W., Quairiaux, C., Genoud, C. & Welker, E. Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34, 265–273 (2002)

    CAS  Article  Google Scholar 

  16. 16

    Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory formation. Annu. Rev. Physiol. 55, 397–426 (1993)

    CAS  Article  Google Scholar 

  17. 17

    Harris, K. M. Structure, development, and plasticity of dendritic spines. Curr. Opin. Neurobiol. 9, 343–348 (1999)

    CAS  Article  Google Scholar 

  18. 18

    Nimchinsky, E. A., Sabatini, B. L. & Svoboda, K. Structure and function of dendritic spines. Annu. Rev. Physiol. 64, 313–353 (2002)

    CAS  Article  Google Scholar 

  19. 19

    Maletic-Savatic, M., Malinow, R. & Svoboda, K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927 (1999)

    ADS  CAS  Article  Google Scholar 

  20. 20

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

    ADS  CAS  Article  Google Scholar 

  21. 21

    Toni, N., Buchs, P. A., Nikonenko, I., Bron, C. R. & Muller, D. LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425 (1999)

    ADS  CAS  Article  Google Scholar 

  22. 22

    Yankova, M., Hart, S. A. & Woolley, C. S. Estrogen increases synaptic connectivity between single presynaptic inputs and multiple postsynaptic CA1 pyramidal cells: A serial electron-microscopic study. Proc. Natl Acad. Sci. USA 98, 3525–3530 (2001)

    ADS  CAS  Article  Google Scholar 

  23. 23

    Lendvai, B., Stern, E., Chen, B. & Svoboda, K. Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–881 (2000)

    ADS  CAS  Article  Google Scholar 

  24. 24

    Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000)

    CAS  Article  Google Scholar 

  25. 25

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

    ADS  CAS  Article  Google Scholar 

  26. 26

    Denk, W. & Svoboda, K. Photon upmanship: why multiphoton imaging is more than a gimmick. Neuron 18, 351–357 (1997)

    CAS  Article  Google Scholar 

  27. 27

    Kim, H. G. & Connors, B. W. Apical dendrites of the neocortex: correlation between sodium- and calcium-dependent spiking and pyramidal cell morphology. J. Neurosci. 13, 5301–5311 (1993)

    CAS  Article  Google Scholar 

  28. 28

    Vaughn, J. E. & Peters, A. A three dimensional study of layer I of the rat parietal cortex. J. Comp. Neurol. 149, 355–370 (1973)

    Article  Google Scholar 

  29. 29

    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 

  30. 30

    Harris, K. M., Jensen, F. E. & Tsao, B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation. J. Neurosci. 12, 2685–2705 (1992)

    CAS  Article  Google Scholar 

  31. 31

    Wiesel, T. N. The postnatal development of the visual cortex and the influence of environment. Nature 299, 583–591 (1982)

    ADS  CAS  Article  Google Scholar 

  32. 32

    Glazewski, S., McKenna, M., Jacquin, M. & Fox, K. Experience-dependent depression of vibrissae responses in adolescent rat barrel cortex. Eur. J. Neurosci. 10, 2107–2116 (1998)

    CAS  Article  Google Scholar 

  33. 33

    Fox, K. Anatomical pathways and molecular mechanisms for plasticity in the barrel cortex. Neuroscience 111, 799–814 (2002)

    CAS  Article  Google Scholar 

  34. 34

    Stern, E., Maravall, M. & Svoboda, K. Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo. Neuron 31, 305–315 (2001)

    CAS  Article  Google Scholar 

  35. 35

    Zhu, J. J. & Connors, B. W. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. J. Neurophysiol. 81, 1171–1183 (1999)

    CAS  Article  Google Scholar 

  36. 36

    Moore, C. I. & Nelson, S. B. Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80, 2882–2892 (1998)

    CAS  Article  Google Scholar 

  37. 37

    Huttenlocher, P. R., de Courten, C., Garey, L. J. & Van der Loos, H. Synaptogenesis in human visual cortex—evidence for synapse elimination during normal development. Neurosci. Lett. 33, 247–252 (1982)

    CAS  Article  Google Scholar 

  38. 38

    Rakic, P., Bourgeois, J. P., Eckenhoff, M. F., Zecevic, N. & Goldman-Rakic, P. S. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232, 232–235 (1986)

    ADS  CAS  Article  Google Scholar 

  39. 39

    Hubel, D. H. & Wiesel, T. N. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophyiol. 26, 1003–1017 (1963)

    Article  Google Scholar 

  40. 40

    Antonini, A. & Stryker, M. P. Rapid remodeling of axonal arbors in the visual cortex. Science 260, 1819–1821 (1993)

    ADS  CAS  Article  Google Scholar 

  41. 41

    Sandison, D. R., Piston, D. W. & Webb, W. W. Three-Dimensional Confocal Microscopy: Volume Investigation of Biological Specimens (eds Stevens, J. K., Mills, L. R. & Trogadis, J. E.) 29–47 (Academic, New York, 1994)

    Google Scholar 

  42. 42

    Harris, K. M. & Stevens, J. K. Dendritic spines of CA1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characterisitcs. J. Neurosci. 9, 2982–2997 (1989)

    CAS  Article  Google Scholar 

  43. 43

    Dunaevsky, A., Blazeski, R., Yuste, R. & Mason, C. Spine motility with synaptic contact. Nature Neurosci. 4, 685–686 (2001)

    CAS  Article  Google Scholar 

Download references


We thank M. Chklovskii for useful discussions, E. Ruthazer, W. Thompson, R. Weinberg and members of our laboratory for a critical reading of the manuscript, T. Pologruto and B. Sabatini for programming, and B. Burbach, P. O'Brien and A. Holtmaat for help with experiments. This work was supported by the Pew, Mathers, and Lehrman Foundations, HFSP and NIH (K.S.), and the Swiss National Science Foundation and HFSP (E.W.). B.C. is a predoctoral student at SUNY Stony Brook.

Author information



Corresponding author

Correspondence to Karel Svoboda.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Trachtenberg, J., Chen, B., Knott, G. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002). https://doi.org/10.1038/nature01273

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

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