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Long-term dendritic spine stability in the adult cortex

Abstract

The structural dynamics of synapses probably has a crucial role in the development and plasticity of the nervous system. In the mammalian brain, the vast majority of excitatory axo-dendritic synapses occur on dendritic specializations called ‘spines’. However, little is known about their long-term changes in the intact developing or adult animal. To address this question we developed a transcranial two-photon imaging technique to follow identified spines of layer-5 pyramidal neurons in the primary visual cortex of living transgenic mice expressing yellow fluorescent protein. Here we show that filopodia-like dendritic protrusions, extending and retracting over hours, are abundant in young animals but virtually absent from the adult. In young mice, within the ‘critical period’ for visual cortex development, 73% of spines remain stable over a one-month interval; most changes are associated with spine elimination. In contrast, in adult mice, the overwhelming majority of spines (96%) remain stable over the same interval with a half-life greater than 13 months. These results indicate that spines, initially plastic during development, become remarkably stable in the adult, providing a potential structural basis for long-term information storage.

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Figure 1: Transcranial two-photon imaging in young animals shows dynamic dendritic filopodia.
Figure 2: Dendrites in young (1-month-old) animals show predominantly spine and filopodia elimination over long intervals.
Figure 3: Dendritic spines in adult mice demonstrate long-term stability.
Figure 4: Spine stability increases with age.

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References

  1. 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 

  2. Rakic, P., Bourgeois, J. P. & Goldman-Rakic, P. S. Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness. Prog. Brain Res. 102, 227–243 (1994)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Florence, S. L., Taub, H. B. & Kaas, J. H. Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys. Science 6, 1117–1121 (1998)

    Article  ADS  Google Scholar 

  6. Jones, E. G. & Pons, T. P. Thalamic and brainstem contributions to large-scale plasticity of primate somatosensory cortex. Science 282, 1121–1125 (1998)

    Article  ADS  CAS  Google Scholar 

  7. Lund, J. S., Boothe, R. G. & Lund, R. D. Development of neurons in the visual cortex (area 17) of the monkey (Macaca nemestrina): a Golgi study from fetal day 127 to postnatal maturity. J. Comp. Neurol. 176, 149–188 (1977)

    Article  CAS  Google Scholar 

  8. 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 11, 232–235 (1986)

    Article  ADS  Google Scholar 

  9. 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 

  10. Antonini, A., Fagiolini, M. & Stryker, M. P. Anatomical correlates of functional plasticity in mouse visual cortex. J. Neurosci. 1, 4388–4406 (1999)

    Article  Google Scholar 

  11. Bao, S., Chan, V. T. & Merzenich, M. M. Cortical remodelling induced by activity of ventral tegmental dopamine neurons. Nature 412, 79–83 (2001)

    Article  ADS  CAS  Google Scholar 

  12. Kleim, J. A. et al. Selective synaptic plasticity within the cerebellar cortex following complex motor skill learning. Neurobiol. Learn. Mem. 69, 274–289 (1998)

    Article  CAS  Google Scholar 

  13. 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  Google Scholar 

  14. 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 

  15. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  17. Dailey, M. E. & Smith, S. J. The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. 16, 2983–2994 (1996)

    Article  CAS  Google Scholar 

  18. 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 

  19. 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 

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

    Article  ADS  CAS  Google Scholar 

  21. Boothe, R. G., Greenough, W. T., Lund, J. S. & Wrege, K. A quantitative investigation of spine and dendrite development of neurons in visual cortex (area 17) of Macaca nemestrina monkeys. J. Comp. Neurol. 186, 473–489 (1979)

    Article  CAS  Google Scholar 

  22. Huttenlocher, P. R. & de Courten, C. The development of synapses in striate cortex of man. Hum. Neurobiol. 6, 1–9 (1987)

    CAS  PubMed  Google Scholar 

  23. Bourgeois, J. P., Goldman-Rakic, P. S. & Rakic, P. Synaptogenesis in the prefrontal cortex of rhesus monkeys. Cereb. Cortex 4, 78–96 (1994)

    Article  CAS  Google Scholar 

  24. Harris, K. M. & Stevens, J. K. Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982–2997 (1989)

    Article  CAS  Google Scholar 

  25. Murthy, V. N., Schikorski, T., Stevens, C. F. & Zhu, Y. Inactivity produces increases in neurotransmitter release and synapse size. Neuron 32, 673–682 (2001)

    Article  CAS  Google Scholar 

  26. 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 

  27. Purves, D., Voyvodic, J. T., Magrassi, L. & Yawo, H. Nerve terminal remodeling visualized in living mice by repeated examination of the same neuron. Science 238, 1122–1126 (1987)

    Article  ADS  CAS  Google Scholar 

  28. Lichtman, J. W., Magrassi, L. & Purves, D. Visualization of neuromuscular junctions over periods of several months in living mice. J. Neurosci. 7, 1215–1222 (1987)

    Article  CAS  Google Scholar 

  29. Majewska, A., Yiu, G. & Yuste, R. A custom-made two-photon microscope and deconvolution system. Pflügers Arch. Eur. J. Physiol. 441, 398–408 (2000)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank J. Lichtman, S. Burden and R. Yuste for critical comments on this manuscript. This work was supported by grants from the National Institutes of Health and the Ellison Foundation to W.-B.G. and by an Irene Diamond grant to M. L. Dustin for purchasing the imaging system.

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Correspondence to Wen-Biao Gan.

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Grutzendler, J., Kasthuri, N. & Gan, WB. Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002). https://doi.org/10.1038/nature01276

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