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Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex

Nature Neuroscience volume 9, pages 660–668 (2006)Cite this article

Abstract

Two key models for examining activity-dependent development of primary visual cortex (V1) involve either reduction of activity in both eyes via dark-rearing (DR) or imbalance of activity between the two eyes via monocular deprivation (MD). Combining DNA microarray analysis with computational approaches, RT-PCR, immunohistochemistry and physiological imaging, we find that DR leads to (i) upregulation of genes subserving synaptic transmission and electrical activity, consistent with a coordinated response of cortical neurons to reduction of visual drive, and (ii) downregulation of parvalbumin expression, implicating parvalbumin-expressing interneurons as underlying the delay in cortical maturation after DR. MD partially activates homeostatic mechanisms but differentially upregulates molecular pathways related to growth factors and neuronal degeneration, consistent with reorganization of connections after MD. Expression of a binding protein of insulin-like growth factor-1 (IGF1) is highly upregulated after MD, and exogenous application of IGF1 prevents the physiological effects of MD on ocular dominance plasticity examined in vivo.

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Figure 1: Analysis and characterization of genes activated by different protocols of visual input deprivation.
Figure 2: Regulation of genes involved in excitatory and inhibitory transmission after MD and DR.
Figure 3: Confirmation of selected genes with RT-PCR.
Figure 4: Gene set enrichment analysis of gene expression after DR and MD.
Figure 5: Protein expression analyses of selected molecules after DR and MD.
Figure 6: Application of IGF1 prevents the ocular dominance shift after MD in mouse V1.
Figure 7: Immunohistochemistry studies for selected markers of the IGF1 pathway.

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Acknowledgements

We thank members of the Sur lab for their assistance, comments and advice and the staff at the Massachusetts Institute of Technology BioMicro Center for processing the RNA samples and for advice on data analysis. Supported by a National Research Service Award fellowship from the US National Institutes of Health (D.T.), a McGovern Fellowship (G.K.) and grants from the NIH and the Simons Foundation (M.S.).

Author information

Author notes

  1. Alvin Lyckman

    Present address: Tufts School of Medicine, Caritas St. Elizabeth's Medical Center, Center for Biomedical Research 406, 736 Cambridge Street, Brighton, Massachusetts, 02135-2997, USA

  2. Sayan Mukherjee

    Present address: Institute for Genome Sciences and Policy, CIEMAS, Duke University, 101 Science Drive, Box 3382, Durham, North Carolina, 27708, USA

Authors and Affiliations

  1. Department of Brain and Cognitive Sciences and Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Daniela Tropea, Alvin Lyckman, Hongbo Yu, Sam Horng & Mriganka Sur

  2. Department of Brain and Cognitive Sciences and McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Gabriel Kreiman & Sayan Mukherjee

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Supplementary information

Supplementary Fig. 1

Graphic representation of the Microarray Expression Levels (MEL) for specific GABAergic and Glutamatergic receptors. (PDF 54 kb)

Supplementary Fig. 2

Immunostaining for several interneuron markers in three different conditions: control (Con), Monocular Deprivation (MD) and Dark Rearing (DR). (PDF 131 kb)

Supplementary Fig. 3

Comparison of gene expression in: (A) Short-term MD (4 days, P23-27) – expression in contralateral cortex versus control; (B) Short-term MD (4 days, P23-27) – expression in ipsilateral cortex versus control. (PDF 71 kb)

Supplementary Fig. 4

Double staining for IGFBP5 (green) and GAD67 (red) in visual cortex of a P28 mouse. (PDF 122 kb)

Supplementary Fig. 5

Comparison of gene expression in (A) Short-term MD+IGF1 versus control; (B) Short-term MD versus Short-term MD+IGF1. (PDF 29 kb)

Supplementary Table 1

Representation of the biological function categories at level 3 of the Gene Ontology (GO) database. (PDF 50 kb)

Supplementary Table 2

Representation of the number of genes significantly (P<0.01) up- and down- regulated across different conditions. (PDF 67 kb)

Supplementary Table 3

Representation of the top Gene Sets enriched in DR (left column) and MD (right column) versus control. (PDF 68 kb)

Supplementary Table 4

Representation of the top Gene Sets enriched in control versus the deprived conditions. (PDF 223 kb)

Supplementary Methods (DOC 59 kb)

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Tropea, D., Kreiman, G., Lyckman, A. et al. Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex. Nat Neurosci 9, 660–668 (2006). https://doi.org/10.1038/nn1689

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