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.
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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.
Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
This file contains Supplementary Notes 1 and 2, Supplementary Discussion 1 and 2, Supplementary Methods and Supplementary References (PDF 37 kb)
Survival function (PDF 91 kb)
Location-dependent growth of persistent spines. (PDF 196 kb)
New spine growth. (PDF 100 kb)
Examples of complex-tuft and simple-tuft cells and correlations. (PDF 126 kb)
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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
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