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.

Stably maintained dendritic spines are associated with lifelong memories


Changes in synaptic connections are considered essential for learning and memory formation1,2,3,4,5,6. However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in the mouse cortex7,8, that learning and novel sensory experience lead to spine formation and elimination by a protracted process. The extent of spine remodelling correlates with behavioural improvement after learning, suggesting a crucial role of synaptic structural plasticity in memory formation. Importantly, a small fraction of new spines induced by novel experience, together with most spines formed early during development and surviving experience-dependent elimination, are preserved and provide a structural basis for memory retention throughout the entire life of an animal. These studies indicate that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


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

Figure 1: Motor learning and novel sensory experience promote rapid dendritic spine formation.
Figure 2: A fraction of newly formed spines persists over weeks and correlates with performance after learning.
Figure 3: Novel experience promotes spine elimination.
Figure 4: Maintenance of daily formed new spines and spines formed during early development throughout life.
Figure 5: Spine maintenance in different cell types and cortical layers.


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

    Article  CAS  Google Scholar 

  2. Buonomano, D. V. & Merzenich, M. M. Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998)

    Article  CAS  Google Scholar 

  3. Changeux, J. P. & Danchin, A. Selective stabilisation of developing synapses as a mechanism for the specification of neuronal networks. Nature 264, 705–712 (1976)

    Article  ADS  CAS  Google Scholar 

  4. Hubel, D. H., Wiesel, T. N. & LeVay, S. Plasticity of ocular dominance columns in monkey striate cortex. Phil. Trans. R. Soc. Lond. B 278, 377–409 (1977)

    Article  ADS  CAS  Google Scholar 

  5. Lichtman, J. W. & Colman, H. Synapse elimination and indelible memory. Neuron 25, 269–278 (2000)

    Article  CAS  Google Scholar 

  6. Shatz, C. J. & Stryker, M. P. Ocular dominance in layer IV of the cat’s visual cortex and the effects of monocular deprivation. J. Physiol. (Lond.) 281, 267–283 (1978)

    Article  CAS  Google Scholar 

  7. Grutzendler, J., Kasthuri, N. & Gan, W. B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002)

    Article  ADS  CAS  Google Scholar 

  8. Zuo, Y., Lin, A., Chang, P. & Gan, W. B. Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46, 181–189 (2005)

    Article  CAS  Google Scholar 

  9. Zuo, Y., Yang, G., Kwon, E. & Gan, W. B. Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436, 261–265 (2005)

    Article  ADS  CAS  Google Scholar 

  10. Purves, D. & Hadley, R. D. Changes in the dendritic branching of adult mammalian neurones revealed by repeated imaging in situ . Nature 315, 404–406 (1985)

    Article  ADS  CAS  Google Scholar 

  11. Trachtenberg, J. T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788–794 (2002)

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  13. Sin, W. C., Haas, K., Ruthazer, E. S. & Cline, H. T. Dendrite growth increased by visual activity requires NMDA receptor and Rho GTPases. Nature 419, 475–480 (2002)

    Article  ADS  CAS  Google Scholar 

  14. Kleim, J. A., Vij, K., Ballard, D. H. & Greenough, W. T. Learning-dependent synaptic modifications in the cerebellar cortex of the adult rat persist for at least four weeks. J. Neurosci. 17, 717–721 (1997)

    Article  CAS  Google Scholar 

  15. Hofer, S. B., Mrsic-Flogel, T. D., Bonhoeffer, T. & Hubener, M. Experience leaves a lasting structural trace in cortical circuits. Nature 457, 313–317 (2009)

    Article  ADS  CAS  Google Scholar 

  16. Holtmaat, A., Wilbrecht, L., Knott, G. W., Welker, E. & Svoboda, K. Experience-dependent and cell-type-specific spine growth in the neocortex. Nature 441, 979–983 (2006)

    Article  ADS  CAS  Google Scholar 

  17. Dunaevsky, A., Tashiro, A., Majewska, A., Mason, C. & Yuste, R. Developmental regulation of spine motility in the mammalian central nervous system. Proc. Natl Acad. Sci. USA 96, 13438–13443 (1999)

    Article  ADS  CAS  Google Scholar 

  18. Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. & Kasai, H. M. Structural basis of long-term potentiation in single dendritic spines. Nature 429, 761–766 (2004)

    Article  ADS  CAS  Google Scholar 

  19. 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)

    Article  ADS  CAS  Google Scholar 

  20. Costa, R. M., Cohen, D. & Nicolelis, M. A. Differential corticostriatal plasticity during fast and slow motor skill learning in mice. Curr. Biol. 14, 1124–1134 (2004)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  22. Karni, A. et al. The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. Proc. Natl Acad. Sci. USA 95, 861–868 (1998)

    Article  ADS  CAS  Google Scholar 

  23. Buitrago, M. M., Schulz, J. B., Dichgans, J. & Luft, A. R. Short and long-term motor skill learning in an accelerated rotarod training paradigm. Neurobiol. Learn. Mem. 81, 211–216 (2004)

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Karni, A. & Sagi, D. The time course of learning a visual skill. Nature 365, 250–252 (1993)

    Article  ADS  CAS  Google Scholar 

  26. Celikel, T. & Sakmann, B. Sensory integration across space and in time for decision making in the somatosensory system of rodents. Proc. Natl Acad. Sci. USA 104, 1395–1400 (2007)

    Article  ADS  CAS  Google Scholar 

  27. Arenz, A., Silver, R. A., Schaefer, A. T. & Margrie, T. W. The contribution of single synapses to sensory representation in vivo . Science 321, 977–980 (2008)

    Article  ADS  CAS  Google Scholar 

  28. Houweling, A. R. & Brecht, M. Behavioural report of single neuron stimulation in somatosensory cortex. Nature 451, 65–68 (2008)

    Article  ADS  CAS  Google Scholar 

  29. Huttenlocher, P. R. & Dabholkar, A. S. Regional differences in synaptogenesis in human cerebral cortex. J. Comp. Neurol. 387, 167–178 (1997)

    Article  CAS  Google Scholar 

  30. 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)

    Article  ADS  CAS  Google Scholar 

  31. Li, C. X. & Waters, R. S. Organization of the mouse motor cortex studied by retrograde tracing and intracortical microstimulation (ICMS) mapping. Can. J. Neurol. Sci. 18, 28–38 (1991)

    Article  CAS  Google Scholar 

  32. Anderson, B. J., Eckburg, P. B. & Relucio, K. I. Alterations in the thickness of motor cortical subregions after motor-skill learning and exercise. Learn. Mem. 9, 1–9 (2002)

    Article  Google Scholar 

  33. Diamond, M. C. et al. Increases in cortical depth and glia numbers in rats subjected to enriched environment. J. Comp. Neurol. 128, 117–126 (1966)

    Article  CAS  Google Scholar 

  34. Grossman, A. W., Churchill, J. D., Bates, K. E., Kleim, J. A. & Greenough, W. T. A brain adaptation view of plasticity: is synaptic plasticity an overly limited concept? Prog. Brain Res. 138, 91–108 (2002)

    Article  Google Scholar 

  35. Kleim, J. A., Pipitone, M. A., Czerlanis, C. & Greenough, W. T. Structural stability within the lateral cerebellar nucleus of the rat following complex motor learning. Neurobiol. Learn. Mem. 69, 290–306 (1998)

    Article  CAS  Google Scholar 

Download references


This work was supported by National Institutes of Health R01 NS047325 and a Dart Foundation Fellowship to W.-B.G. and by an Ellison/AFAR Postdoctoral Fellowship to G.Y. We thank members of the Gan laboratory for their comments.

Author Contributions G.Y. and W.-B.G. conceived the experiments. G.Y. performed and analysed most experiments on motor cortex and all the experiments on barrel cortex. F.P. conducted and analysed some of the experiments on motor cortex. G.Y. and W.-B.G. performed the data fitting. W.-B.G. wrote the manuscript.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Wen-Biao Gan.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-7 with Legends, Supplementary Tables a and b, Supplementary Data, a Supplementary Discussion and Supplementary References. (PDF 539 kb)

Supplementary Movie 1

This movie file shows mice in Cage 1 which is a bead-string hanging enriched cage in which 200 strings of plastic beads were evenly hung from the top of the cage grid. The mice need to navigate through the bead-strings to get access to food and water. (MOV 8759 kb)

Supplementary Movie 2

This movie file shows mice in Cage 2 which is a bead-string hanging enriched cage in which 200 strings of plastic beads were evenly hung from the top of the cage grid. The mice need to navigate through the bead-strings to get access to food and water. (MOV 9169 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yang, G., Pan, F. & Gan, WB. Stably maintained dendritic spines are associated with lifelong memories . Nature 462, 920–924 (2009).

Download citation

  • Received:

  • Accepted:

  • Published:

  • 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