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Effects of visual experience on activity-dependent gene regulation in cortex

Abstract

There are critical periods in development when sensory experience directs the maturation of synapses and circuits within neocortex. We report that the critical period in mouse visual cortex has a specific molecular logic of gene regulation. Four days of visual deprivation regulated one set of genes during the critical period, and different sets before or after. Dark rearing perturbed the regulation of these age-specific gene sets. In addition, a 'common gene set', comprised of target genes belonging to a mitogen-activated protein (MAP) kinase signaling pathway, was regulated by vision at all ages but was impervious to prior history of sensory experience. Together, our results demonstrate that vision has dual effects on gene regulation in visual cortex and that sensory experience is needed for the sequential acquisition of age-specific, but not common, gene sets. Thus, a dynamic interplay between experience and gene expression drives activity-dependent circuit maturation.

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Figure 1: Mouse visual system connections and gene regulation by 4 d of visual deprivation.
Figure 2: Visual input regulates a common gene set and age-specific gene sets.
Figure 3: Validation of regulated gene set by real-time PCR and in situ hybridization.
Figure 4: Visual deprivation regulates the common gene set via MEK1/2 signaling.
Figure 5: Microarray comparison of genes regulated by vision at P46 in normally reared versus dark-reared mice.
Figure 6: Real-time PCR confirms altered gene regulation in dark-reared cortex at P46.
Figure 7: Short periods of dark rearing alter gene regulation.

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Acknowledgements

We wish to thank M. Marcotrigiano, B. Printseva and Y. Kim for expert surgical, histological and technical assistance, C. Weitz and H. Zoghbi for their critical reading of the manuscript, Y. Tagawa for generously sharing his reagents and expertise, and members of the Shatz lab for helpful discussions. This work was supported by grants from the US National Institutes of Health (NEI R01 and EY02858) to C.J.S. and by Canadian Institutes of Health Research and Harvard Medical School Berenberg Fellowships to M.M.

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Correspondence to Carla J Shatz.

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Supplementary information

Supplementary Table 1

Expression levels of many age-specific regulated genes remain constant during development. (PDF 50 kb)

Supplementary Table 2

Primer sets used for cloning. (PDF 45 kb)

Supplementary Table 3

Primer sets used for real-time PCR analysis. (PDF 59 kb)

Supplementary Methods (PDF 57 kb)

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Majdan, M., Shatz, C. Effects of visual experience on activity-dependent gene regulation in cortex. Nat Neurosci 9, 650–659 (2006). https://doi.org/10.1038/nn1674

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