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:

Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning

Abstract

Behavioural learning depends on the brain’s capacity to respond to instructive experience and is often enhanced during a juvenile sensitive period. How instructive experience acts on the juvenile brain to trigger behavioural learning remains unknown. In vitro studies show that forms of synaptic strengthening thought to underlie learning are accompanied by an increase in the stability, number and size of dendritic spines, which are the major sites of excitatory synaptic transmission in the vertebrate brain1,2,3,4,5,6,7. In vivo imaging studies in sensory cortical regions reveal that these structural features can be affected by disrupting sensory experience and that spine turnover increases during sensitive periods for sensory map formation8,9,10,11,12. These observations support two hypotheses: first, the increased capacity for behavioural learning during a sensitive period is associated with enhanced spine dynamics on sensorimotor neurons important for the learned behaviour; second, instructive experience rapidly stabilizes and strengthens these dynamic spines. Here we report a test of these hypotheses using two-photon in vivo imaging to measure spine dynamics in zebra finches, which learn to sing by imitating a tutor song during a juvenile sensitive period13,14. Spine dynamics were measured in the forebrain nucleus HVC, the proximal site where auditory information merges with an explicit song motor representation15,16,17,18,19, immediately before and after juvenile finches first experienced tutor song20. Higher levels of spine turnover before tutoring correlated with a greater capacity for subsequent song imitation. In juveniles with high levels of spine turnover, hearing a tutor song led to the rapid (24-h) stabilization, accumulation and enlargement of dendritic spines in HVC. Moreover, in vivo intracellular recordings made immediately before and after the first day of tutoring revealed robust enhancement of synaptic activity in HVC. These findings suggest that behavioural learning results when instructive experience is able to rapidly stabilize and strengthen synapses on sensorimotor neurons important for the control of the learned behaviour.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Examining how tutor song affects spine turnover in juvenile zebra finches.
Figure 2: Levels of HVC dendritic spine turnover correlate with song imitation.
Figure 3: Tutoring can trigger rapid stabilization and accumulation of dendritic spines on HVC neurons.
Figure 4: Tutoring triggers enlargement of stable dendritic spines in HVC.
Figure 5: Tutoring triggers enhancement of spontaneous synaptic activity in HVC.

Similar content being viewed by others

References

  1. 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 

  2. De Roo, M., Klauser, P. & Muller, D. LTP promotes a selective long-term stabilization and clustering of dendritic spines. PLoS Biol. 6, e219 (2008)

    Article  Google Scholar 

  3. Chklovskii, D. B., Mel, B. W. & Svoboda, K. Cortical rewiring and information storage. Nature 431, 782–788 (2004)

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  5. Alvarez, V. A. & Sabatini, B. L. Anatomical and physiological plasticity of dendritic spines. Annu. Rev. Neurosci. 30, 79–97 (2007)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  7. Zito, K., Scheuss, V., Knott, G., Hill, T. & Svoboda, K. Rapid functional maturation of nascent dendritic spines. Neuron 61, 247–258 (2009)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  9. Majewska, A. & Sur, M. Motility of dendritic spines in visual cortex in vivo: changes during the critical period and effects of visual deprivation. Proc. Natl Acad. Sci. USA 100, 16024–16029 (2003)

    Article  ADS  CAS  Google Scholar 

  10. 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 

  11. 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 

  12. 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 

  13. Eales, L. A. Song learning in zebra finches: some effects of song model availability on what is learnt and when. Anim. Behav. 33, 1293–1300 (1985)

    Article  Google Scholar 

  14. Immelmann, K. in Bird Vocalisations (ed. Hinde, R. A.) 61–74 (Cambridge Univ. Press, 1969)

    Google Scholar 

  15. Prather, J. F., Peters, S., Nowicki, S. & Mooney, R. Precise auditory-vocal mirroring in neurons for learned vocal communication. Nature 451, 305–310 (2008)

    Article  ADS  CAS  Google Scholar 

  16. Bauer, E. E. et al. A synaptic basis for auditory-vocal integration in the songbird. J. Neurosci. 28, 1509–1522 (2008)

    Article  CAS  Google Scholar 

  17. McCasland, J. S. & Konishi, M. Interaction between auditory and motor activities in an avian song control nucleus. Proc. Natl Acad. Sci. USA 78, 7815–7819 (1981)

    Article  ADS  CAS  Google Scholar 

  18. Nottebohm, F., Stokes, T. M. & Leonard, C. M. Central control of song in the canary, Serinus canarius . J. Comp. Neurol. 165, 457–486 (1976)

    Article  CAS  Google Scholar 

  19. Hahnloser, R. H. R., Kozhevnikov, A. A. & Fee, M. S. An ultra-sparse code underlies the generation of neural sequences in a songbird. Nature 419, 65–70 (2002)

    Article  ADS  CAS  Google Scholar 

  20. Tchernichovski, O., Mitra, P. P., Lints, T. & Nottebohm, F. Dynamics of the vocal imitation process: how a zebra finch learns its song. Science 291, 2564–2569 (2001)

    Article  ADS  CAS  Google Scholar 

  21. Roberts, T. F., Klein, M. E., Kubke, M. F., Wild, J. M. & Mooney, R. Telencephalic neurons monosynaptically link brainstem and forebrain premotor networks necessary for song. J. Neurosci. 28, 3479–3489 (2008)

    Article  CAS  Google Scholar 

  22. Dittgen, T. et al. Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo . Proc. Natl Acad. Sci. USA 101, 18206–18211 (2004)

    Article  ADS  CAS  Google Scholar 

  23. Mooney, R. Different subthreshold mechanisms underlie song-selectivity in identified HVc neurons of the zebra finch. J. Neurosci. 20, 5420–5436 (2000)

    Article  CAS  Google Scholar 

  24. Scharff, C., Kirn, J. R., Grossman, M., Macklis, J. D. & Nottebohm, F. Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds. Neuron 25, 481–492 (2000)

    Article  CAS  Google Scholar 

  25. 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 

  26. Derégnaucourt, S., Mitra, P. P., Feher, O., Pytte, C. & Tchernichovski, O. How sleep affects the developmental learning of bird song. Nature 433, 710–716 (2005)

    Article  ADS  Google Scholar 

  27. 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 

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

    Article  CAS  Google Scholar 

  29. Shank, S. S. & Margoliash, D. Sleep and sensorimotor integration during early vocal learning in a songbird. Nature 458, 73–77 (2009)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Ehlers and L. Katz for access to the two-photon microscope and support in making lentivirus, K. Hamaguchi for peak detection and analysis software and D. Kloetzer for animal husbandry and laboratory support. D. Fitzpatrick, D. Purves and M. Ehlers provided comments on the manuscript. This work was supported by grants from the US National Science Foundation (NSF) and the US National Institutes of Health (NIH) (R.M.). T.F.R. was supported by a National Research Service Award from the NIH, K.A.T. was supported by a pre-doctoral award from the NSF and M.E.K. was supported by the Howard Hughes Medical Institute (Investigator, M. Ehlers).

Author Contributions T.F.R. and R.M. designed the study and wrote the manuscript. T.F.R. and K.A.T. collected and analysed the imaging and behavioural data. T.F.R. and M.E.K. designed the lentiviral construct and M.E.K. made the lentivirus. T.F.R and R.M. collected the electrophysiological data.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard Mooney.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Table 1 and Supplementary Figures 1-4 with Legends. (PDF 915 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roberts, T., Tschida, K., Klein, M. et al. Rapid spine stabilization and synaptic enhancement at the onset of behavioural learning. Nature 463, 948–952 (2010). https://doi.org/10.1038/nature08759

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature08759

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

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