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Rapid formation and selective stabilization of synapses for enduring motor memories


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.

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Figure 1: Motor skill learning in adolescent mice promotes immediate spine formation in the contralateral motor cortex.
Figure 2: Enhanced spine dynamics during adolescent motor training is region- and learning-specific.
Figure 3: Motor skill learning stabilizes newly formed spines.
Figure 4: Novel motor skill training promotes spine formation and elimination in adult mice.


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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.

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Correspondence to Yi Zuo.

Supplementary information

Supplementary Information

This file contains Supplementary Notes, Supplementary References, Supplementary Figures 1-5 with Legends and Supplementary Table S1. (PDF 2218 kb)

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. (MOV 4465 kb)

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Xu, T., Yu, X., Perlik, A. et al. Rapid formation and selective stabilization of synapses for enduring motor memories. Nature 462, 915–919 (2009).

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