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-dependent and cell-type-specific spine growth in the neocortex

Nature volume 441, pages 979–983 (2006)Cite this article

Abstract

Functional circuits in the adult neocortex adjust to novel sensory experience, but the underlying synaptic mechanisms remain unknown1. Growth and retraction of dendritic spines with synapse formation and elimination could change brain circuits2,3,4,5,6,7. In the apical tufts of layer 5B (L5B) pyramidal neurons in the mouse barrel cortex, a subset of dendritic spines appear and disappear over days, whereas most spines are persistent for months4,5,6,8,9. Under baseline conditions, new spines are mostly transient and rarely survive for more than a week. Transient spines tend to be small4,5,9, whereas persistent spines are usually large4,5,6,8,9. Because most excitatory synapses in the cortex occur on spines, and because synapse size10 and the number of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors11,12,13 are proportional to spine volume, the excitation of pyramidal neurons is probably driven through synapses on persistent spines. Here we test whether the generation and loss of persistent spines are enhanced by novel sensory experience. We repeatedly imaged dendritic spines for one month after trimming alternate whiskers, a paradigm that induces adaptive functional changes in neocortical circuits14,15. Whisker trimming stabilized new spines and destabilized previously persistent spines. New-persistent spines always formed synapses. They were preferentially added on L5B neurons with complex apical tufts rather than simple tufts. Our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons. These synaptic changes probably underlie experience-dependent remodelling of specific neocortical circuits.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: Retraction and growth of persistent spines.
Figure 2: Spine stabilization and destabilization.
Figure 3: Cell-type-dependent growth of persistent spines.

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. 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)

    Article  CAS  PubMed  Google Scholar 

  4. 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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. 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  PubMed  Google Scholar 

  7. De Paola, V. et al. Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex. Neuron 49, 861–875 (2006)

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  9. 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  PubMed  Google Scholar 

  10. 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)

    Article  CAS  PubMed  Google Scholar 

  11. Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545–559 (1998)

    Article  CAS  PubMed  Google Scholar 

  12. Takumi, Y., Ramirez-Leon, V., Laake, P., Rinvik, E. & Ottersen, O. P. Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nature Neurosci. 2, 618–624 (1999)

    Article  CAS  PubMed  Google Scholar 

  13. Matsuzaki, M. et al. Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nature Neurosci. 4, 1086–1092 (2001)

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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  PubMed  Google Scholar 

  19. Glazewski, S. & Fox, K. Time course of experience-dependent synaptic potentiation and depression in barrel cortex of adolescent rats. J. Neurophysiol. 75, 1714–1729 (1996)

    Article  CAS  PubMed  Google Scholar 

  20. Shepherd, G. M., Pologruto, T. A. & Svoboda, K. Circuit analysis of experience-dependent plasticity in the developing rat barrel cortex. Neuron 38, 277–289 (2003)

    Article  CAS  PubMed  Google Scholar 

  21. Lu, S. M. & Lin, R. C. S. Thalamic afferents of the rat barrel cortex: a light- and electron-microscopic study using Phaseolus vulgaris leucoagglutinin as an anterograde tracer. Somatosens. Mot. Res. 10, 1–16 (1993)

    Article  CAS  PubMed  Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. Yuste, R. & Bonhoeffer, T. Genesis of dendritic spines: insights from ultrastructural and imaging studies. Nature Rev. Neurosci. 5, 24–34 (2004)

    Article  CAS  Google Scholar 

  24. Jontes, J. D. & Smith, S. J. Filopodia, spines, and the generation of synaptic diversity. Neuron 27, 11–14 (2000)

    Article  CAS  PubMed  Google Scholar 

  25. Chagnac-Amitai, Y., Luhmann, H. J. & Prince, D. A. Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features. J. Comp. Neurol. 296, 598–613 (1990)

    Article  CAS  PubMed  Google Scholar 

  26. Larkman, A. & Mason, A. Correlations between morphology and electrophysiology of pyramidal neurons in slices of rat visual cortex. I. Establishment of cell classes. J. Neurosci. 10, 1407–1414 (1990)

    Article  CAS  PubMed  Google Scholar 

  27. Kasper, E. M., Larkman, A. U., Lubke, J. & Blakemore, C. Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell morphology, intrinsic electrophysiological properties, and axon targets. J. Comp. Neurol. 339, 459–474 (1994)

    Article  CAS  PubMed  Google Scholar 

  28. Tsiola, A., Hamzei-Sichani, F., Peterlin, Z. & Yuste, R. Quantitative morphologic classification of layer 5 neurons from mouse primary visual cortex. J. Comp. Neurol. 461, 415–428 (2003)

    Article  PubMed  Google Scholar 

  29. Pologruto, T. A., Sabatini, B. L. & Svoboda, K. ScanImage: Flexible software for operating laser-scanning microscopes. Biomed. Eng. Online 2, 13 (2003)

    Article  PubMed  Google Scholar 

  30. Fiala, J. C., Feinberg, M., Popov, V. & Harris, K. M. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J. Neurosci. 18, 8900–8911 (1998)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank L. Petreanu for suggesting the comparison of cell types; V. DePaola, B. Burbach and C. Musetti for help with experiments; K. Masback for data analysis; T. O'Connor for writing the spine analysis software; and V. DePaola, G. Shepherd, J. Trachtenberg and K. Zito for comments on the manuscript. This work was supported by the Howard Hughes Medical Institute, the NIH and the Swiss National Science Foundation (G.W.K, E.W.).Author Contributions A.H. and L.W. contributed equally to this work. A.H. and L.W. performed the imaging experiments. K.S. built the custom microscope. G.W.K. performed the ssEM reconstructions with help from A.H. and L.W. G.W.K., A.H. and L.W. performed the cell reconstructions. A.H., L.W. and K.S. analysed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA

    Anthony Holtmaat, Linda Wilbrecht & Karel Svoboda

  2. Institut de biologie cellulaire et de morphologie (IBCM), Université de Lausanne, Lausanne, Rue du Bugnon 9, CH 1005, Switzerland

    Graham W. Knott & Egbert Welker

Authors
  1. Anthony Holtmaat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linda Wilbrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graham W. Knott
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Egbert Welker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karel Svoboda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karel Svoboda.

Ethics declarations

Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Notes 1 and 2, Supplementary Discussion 1 and 2, Supplementary Methods and Supplementary References (PDF 37 kb)

Supplementary Figure 1

Survival function (PDF 91 kb)

Supplementary Figure 2

Location-dependent growth of persistent spines. (PDF 196 kb)

Supplementary Figure 3

New spine growth. (PDF 100 kb)

Supplementary Figure 4

Examples of complex-tuft and simple-tuft cells and correlations. (PDF 126 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holtmaat, A., Wilbrecht, L., Knott, G. et al. Experience-dependent and cell-type-specific spine growth in the neocortex. Nature 441, 979–983 (2006). https://doi.org/10.1038/nature04783

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature04783

This article is cited by

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