Skip to main content

Thank you for visiting nature.com. 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.

  • Letter
  • Published:

Experience leaves a lasting structural trace in cortical circuits

Nature volume 457, pages 313–317 (2009)Cite this article

Abstract

Sensory experiences exert a powerful influence on the function and future performance of neuronal circuits in the mammalian neocortex1,2,3. Restructuring of synaptic connections is believed to be one mechanism by which cortical circuits store information about the sensory world4,5. Excitatory synaptic structures, such as dendritic spines, are dynamic entities6,7,8 that remain sensitive to alteration of sensory input throughout life6,9. It remains unclear, however, whether structural changes at the level of dendritic spines can outlast the original experience and thereby provide a morphological basis for long-term information storage. Here we follow spine dynamics on apical dendrites of pyramidal neurons in functionally defined regions of adult mouse visual cortex during plasticity of eye-specific responses induced by repeated closure of one eye (monocular deprivation). The first monocular deprivation episode doubled the rate of spine formation, thereby increasing spine density. This effect was specific to layer-5 cells located in binocular cortex, where most neurons increase their responsiveness to the non-deprived eye3,10. Restoring binocular vision returned spine dynamics to baseline levels, but absolute spine density remained elevated and many monocular deprivation-induced spines persisted during this period of functional recovery. However, spine addition did not increase again when the same eye was closed for a second time. This absence of structural plasticity stands out against the robust changes of eye-specific responses that occur even faster after repeated deprivation3. Thus, spines added during the first monocular deprivation experience may provide a structural basis for subsequent functional shifts. These results provide a strong link between functional plasticity and specific synaptic rearrangements, revealing a mechanism of how prior experiences could be stored in cortical circuits.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Monocular deprivation in adult mice increases the rate of spine gain in L5 neurons in binocular cortex.
Figure 2: Monocular deprivation in adult mice does not alter spine dynamics in L2/3 neurons.
Figure 3: MD-induced increase in spine density on L5 neurons outlasts the altered experience.
Figure 4: A second MD increases the size of spines gained during the first MD, without additional spine gain.

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Clark, S. A., Allard, T., Jenkins, W. M. & Merzenich, M. M. Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs. Nature 332, 444–445 (1988)

    Article  ADS  CAS  Google Scholar 

  3. Hofer, S. B., Mrsic-Flogel, T. D., Bonhoeffer, T. & Hübener, M. Prior experience enhances plasticity in adult visual cortex. Nature Neurosci. 9, 127–132 (2006)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Yuste, R. & Bonhoeffer, T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071–1089 (2001)

    Article  CAS  Google Scholar 

  6. 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 

  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. Majewska, A. K., Newton, J. R. & Sur, M. Remodeling of synaptic structure in sensory cortical areas in vivo . J. Neurosci. 26, 3021–3029 (2006)

    Article  CAS  Google Scholar 

  9. Holtmaat, A. J. et al. Transient and persistent dendritic spines in the neocortex in vivo . Neuron 45, 279–291 (2005)

    Article  CAS  Google Scholar 

  10. Sawtell, N. B. et al. NMDA receptor-dependent ocular dominance plasticity in adult visual cortex. Neuron 38, 977–985 (2003)

    Article  CAS  Google Scholar 

  11. Gordon, J. A. & Stryker, M. P. Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. J. Neurosci. 16, 3274–3286 (1996)

    Article  CAS  Google Scholar 

  12. Hensch, T. K. et al. Local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science 282, 1504–1508 (1998)

    Article  CAS  Google Scholar 

  13. Huang, Z. J. et al. BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98, 739–755 (1999)

    Article  CAS  Google Scholar 

  14. Mrsic-Flogel, T. D. et al. Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity. Neuron 54, 961–972 (2007)

    Article  CAS  Google Scholar 

  15. Tagawa, Y., Kanold, P. O., Majdan, M. & Shatz, C. J. Multiple periods of functional ocular dominance plasticity in mouse visual cortex. Nature Neurosci. 8, 380–388 (2005)

    Article  CAS  Google Scholar 

  16. Fischer, Q. S., Graves, A., Evans, S., Lickey, M. E. & Pham, T. A. Monocular deprivation in adult mice alters visual acuity and single-unit activity. Learn. Mem. 14, 277–286 (2007)

    Article  Google Scholar 

  17. Mataga, N., Mizuguchi, Y. & Hensch, T. K. Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron 44, 1031–1041 (2004)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Wang, Q. & Burkhalter, A. Area map of mouse visual cortex. J. Comp. Neurol. 502, 339–357 (2007)

    Article  Google Scholar 

  20. Heimel, J. A., Hartman, R. J., Hermans, J. M. & Levelt, C. N. Screening mouse vision with intrinsic signal optical imaging. Eur. J. Neurosci. 25, 795–804 (2007)

    Article  Google Scholar 

  21. 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 

  22. Knudsen, E. I. Instructed learning in the auditory localization pathway of the barn owl. Nature 417, 322–328 (2002)

    Article  ADS  CAS  Google Scholar 

  23. Linkenhoker, B. A., der Ohe, C. G. & Knudsen, E. I. Anatomical traces of juvenile learning in the auditory system of adult barn owls. Nature Neurosci. 8, 93–98 (2005)

    Article  CAS  Google Scholar 

  24. Knott, G. W., Holtmaat, A., Wilbrecht, L., Welker, E. & Svoboda, K. Spine growth precedes synapse formation in the adult neocortex in vivo . Nature Neurosci. 9, 1117–1124 (2006)

    Article  CAS  Google Scholar 

  25. Nägerl, U. V., Kostinger, G., Anderson, J. C., Martin, K. A. & Bonhoeffer, T. Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons. J. Neurosci. 27, 8149–8156 (2007)

    Article  Google Scholar 

  26. Kasai, H., Matsuzaki, M., Noguchi, J., Yasumatsu, N. & Nakahara, H. Structure-stability-function relationships of dendritic spines. Trends Neurosci. 26, 360–368 (2003)

    Article  CAS  Google Scholar 

  27. Bourne, J. & Harris, K. M. Do thin spines learn to be mushroom spines that remember? Curr. Opin. Neurobiol. 17, 381–386 (2007)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  29. Kopec, C. D., Li, B., Wei, W., Boehm, J. & Malinow, R. Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation. J. Neurosci. 26, 2000–2009 (2006)

    Article  CAS  Google Scholar 

  30. Zhou, Q., Homma, K. J. & Poo, M. M. Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron 44, 749–757 (2004)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank T. Keck for contributing control data for Supplementary Fig. 7a, and M. Sperling and B. Pichler for programming help. This work was supported by the Max Planck Society, the Wellcome Trust and the Humboldt Foundation.

Author information

Author notes

  1. Sonja B. Hofer & Thomas D. Mrsic-Flogel

    Present address: Present address: Department of Physiology, University College London, London WC1 6JJ, UK.,

Authors and Affiliations

  1. Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany

    Sonja B. Hofer, Thomas D. Mrsic-Flogel, Tobias Bonhoeffer & Mark Hübener

Authors
  1. Sonja B. Hofer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas D. Mrsic-Flogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tobias Bonhoeffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Hübener
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Hübener.

Supplementary information

Supplementary Information

This file contains Supplementary Notes, Supplementary References and Supplementary Figures S1-S7 with Legends (PDF 1326 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hofer, S., Mrsic-Flogel, T., Bonhoeffer, T. et al. Experience leaves a lasting structural trace in cortical circuits. Nature 457, 313–317 (2009). https://doi.org/10.1038/nature07487

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature07487

This article is cited by

Comments

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.

Search

Advanced search

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