Letter | Published:

Rapid formation and selective stabilization of synapses for enduring motor memories

Nature volume 462, pages 915919 (17 December 2009) | Download Citation


Novel motor skills are learned through repetitive practice and, once acquired, persist long after training stops1,2. Earlier studies have shown that such learning induces an increase in the efficacy of synapses in the primary motor cortex, the persistence of which is associated with retention of the task3,4,5. However, how motor learning affects neuronal circuitry at the level of individual synapses and how long-lasting memory is structurally encoded in the intact brain remain unknown. Here we show that synaptic connections in the living mouse brain rapidly respond to motor-skill learning and permanently rewire. Training in a forelimb reaching task leads to rapid (within an hour) formation of postsynaptic dendritic spines on the output pyramidal neurons in the contralateral motor cortex. Although selective elimination of spines that existed before training gradually returns the overall spine density back to the original level, the new spines induced during learning are preferentially stabilized during subsequent training and endure long after training stops. Furthermore, we show that different motor skills are encoded by different sets of synapses. Practice of novel, but not previously learned, tasks further promotes dendritic spine formation in adulthood. Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    & Stages of motor skill learning. Mol. Neurobiol. 32, 205–216 (2005)

  2. 2.

    et al. Functional MRI evidence for adult motor cortex plasticity during motor skill learning. Nature 377, 155–158 (1995)

  3. 3.

    , & Plasticity of the synaptic modification range. J. Neurophysiol. 98, 3688–3695 (2007)

  4. 4.

    , & Learning-induced LTP in neocortex. Science 290, 533–536 (2000)

  5. 5.

    , , & Transient spine expansion and learning-induced plasticity in layer 1 primary motor cortex. J. Neurosci. 28, 5686–5690 (2008)

  6. 6.

    , & In search of the motor engram: motor map plasticity as a mechanism for encoding motor experience. Neuroscientist 11, 471–483 (2005)

  7. 7.

    & Plasticity and primary motor cortex. Annu. Rev. Neurosci. 23, 393–415 (2000)

  8. 8.

    , & Long-term dendritic spine stability in the adult cortex. Nature 420, 812–816 (2002)

  9. 9.

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

  10. 10.

    Electron microscopy of synaptic contacts on dendrite spines of the cerebral cortex. Nature 183, 1592–1593 (1959)

  11. 11.

    & Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17, 91–102 (1996)

  12. 12.

    & The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. 16, 2983–2994 (1996)

  13. 13.

    , , & Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436, 261–265 (2005)

  14. 14.

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

  15. 15.

    , , , & Experience-dependent and cell-type-specific spine growth in the neocortex. Nature 441, 979–983 (2006)

  16. 16.

    , , & Experience leaves a lasting structural trace in cortical circuits. Nature 457, 313–317 (2009)

  17. 17.

    et al. Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex. Nature Neurosci. 11, 1162–1167 (2008)

  18. 18.

    , , & Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404, 876–881 (2000)

  19. 19.

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

  20. 20.

    , , , & LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425 (1999)

  21. 21.

    et al. Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J. Neurosci. 24, 628–633 (2004)

  22. 22.

    , , & Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord. J. Appl. Physiol. 101, 1776–1782 (2006)

  23. 23.

    , , , & Rapid functional maturation of nascent dendritic spines. Neuron 61, 247–258 (2009)

  24. 24.

    , , & Learning-dependent synaptic modifications in the cerebellar cortex of the adult rat persist for at least four weeks. J. Neurosci. 17, 717–721 (1997)

  25. 25.

    , & Effects of unilateral and bilateral training in a reaching task on dendritic branching of neurons in the rat motor-sensory forelimb cortex. Behav. Neural Biol. 44, 301–314 (1985)

  26. 26.

    & Reach training selectively alters dendritic branching in subpopulations of layer II–III pyramids in rat motor-somatosensory forelimb cortex. Neuropsychologia 27, 61–69 (1989)

  27. 27.

    et al. Motor learning-dependent synaptogenesis is localized to functionally reorganized motor cortex. Neurobiol. Learn. Mem. 77, 63–77 (2002)

  28. 28.

    , & Contrasting effects of motor and visual spatial learning tasks on dendritic arborization and spine density in rats. Neurobiol. Learn. Mem. 90, 295–300 (2008)

  29. 29.

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

  30. 30.

    , , & Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46, 181–189 (2005)

  31. 31.

    et al. The vermicelli handling test: a simple quantitative measure of dexterous forepaw function in rats. J. Neurosci. Methods 170, 229–244 (2008)

Download references


We thank D. States, W. Thompson, L. Hinck, D. Feldheim, J. Ding, X. Li, A. Lin and C. Cirelli for critical comments on this manuscript; A. Sitko for her pilot studies of skilled reaching in mice, and D. Adkins, J. Kleim and N. Thomas for their assistance with intracortical microstimulation procedures. This work was supported by grants from the Ellison Medical Foundation, the DANA Foundation, and the National Institute on Aging to Y.Z.

Author Contributions T.X. and X.Y. contributed equally to this work. Both of them performed in vivo imaging, analysed the data, made figures and participated in the discussion. A.J.P., W.F.T. and J.A.Z. trained all the mice used in the experiments. K.T. and T.J. developed behavioural methods, performed the intracortical microstimulation experiments, and provided comments for the manuscript. Y.Z. initiated the project, did data analysis and wrote the manuscript.

Author information

Author notes

    • Tonghui Xu
    •  & Xinzhu Yu

    These authors contributed equally to this work.


  1. Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA

    • Tonghui Xu
    • , Xinzhu Yu
    • , Andrew J. Perlik
    • , Willie F. Tobin
    • , Jonathan A. Zweig
    •  & Yi Zuo
  2. Institute for Neuroscience, Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA

    • Kelly Tennant
    •  & Theresa Jones


  1. Search for Tonghui Xu in:

  2. Search for Xinzhu Yu in:

  3. Search for Andrew J. Perlik in:

  4. Search for Willie F. Tobin in:

  5. Search for Jonathan A. Zweig in:

  6. Search for Kelly Tennant in:

  7. Search for Theresa Jones in:

  8. Search for Yi Zuo in:

Corresponding author

Correspondence to Yi Zuo.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Notes, Supplementary References, Supplementary Figures 1-5 with Legends and Supplementary Table S1.


  1. 1.

    Supplementary Movie 1

    This movie file shows a clip of mice during single-seed reaching tasks, showing 3 failed, 1 drop (with a failed reach just before it), and 2 successful reaches.

About this article

Publication history






Further reading


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.