Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex

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Abstract

A substantial decrease in the number of synapses occurs in the mammalian brain from the late postnatal period until the end of life1,2,3,4,5. Although experience plays an important role in modifying synaptic connectivity6,7,8,9,10,11,12,13,14,15,16,17, its effect on this nearly lifelong synapse loss remains unknown. Here we used transcranial two-photon microscopy to visualize postsynaptic dendritic spines in layer I of the barrel cortex in transgenic mice expressing yellow fluorescent protein. We show that in young adolescent mice, long-term sensory deprivation through whisker trimming prevents net spine loss by preferentially reducing the rate of ongoing spine elimination, not by increasing the rate of spine formation. This effect of deprivation diminishes as animals mature but still persists in adulthood. Restoring sensory experience after adolescent deprivation accelerates spine elimination. Similar to sensory manipulation, the rate of spine elimination decreases after chronic blockade of NMDA (N-methyl-d-aspartate) receptors with the antagonist MK801, and accelerates after drug withdrawal. These studies of spine dynamics in the primary somatosensory cortex suggest that experience plays an important role in the net loss of synapses over most of an animal's lifespan, particularly during adolescence.

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Figure 1: Long-term whisker trimming reduces spine elimination in barrel cortex of young adolescent mice at one month of age.
Figure 2: The effect of long-term deprivation on spine elimination decreases but still exists in adulthood.
Figure 3: Restoring sensory experience after previous deprivation accelerates spine elimination in adolescence but not in adulthood.
Figure 4: Spine elimination involves NMDA receptor activation.

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Acknowledgements

We thank N. Kasthuri, W. Thompson and K. Helmin for critical comments on this manuscript. This work was supported by grants from the National Institutes of Health to W.-B.G.

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Correspondence to Wen-Biao Gan.

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Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Data

The effect of chessboard deprivation on spine dynamics in young adolescent and adult barrel cortex. (DOC 66 kb)

Supplementary Table S1

The percentage of spines eliminated and formed over various intervals under different experimental conditions. (DOC 40 kb)

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Zuo, Y., Yang, G., Kwon, E. et al. Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436, 261–265 (2005) doi:10.1038/nature03715

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