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Sensory cortex limits cortical maps and drives top-down plasticity in thalamocortical circuits

Nature Neuroscience volume 16, pages 1060–1067 (2013)Cite this article

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Abstract

The primary somatosensory cortex (S1) contains a complete body map that mirrors the subcortical maps developed by peripheral sensory input projecting to the sensory hindbrain, the thalamus and then S1. Peripheral changes during development alter these maps through 'bottom-up' plasticity. Unknown is how S1 size influences map organization and whether an altered S1 map feeds back to affect subcortical maps. We show that the size of S1 in mice is significantly reduced by cortex-specific deletion of Pax6, resulting in a reduced body map and loss of body representations by an exclusion of later-differentiating sensory thalamocortical input. An initially normal sensory thalamus was repatterned to match the aberrant S1 map by apoptotic deletion of thalamic neurons representing body parts with axons excluded from S1. Deleted representations were rescued by altering competition between thalamocortical axons using sensory deprivation or increasing the size of S1. Thus, S1 size determined the resolution and completeness of body maps and engaged 'top-down' plasticity that repatterned the sensory thalamus to match S1.

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Figure 1: Pax6 specifies S1-area identity in cortical progenitors and determines S1 size.
Figure 2: Quantification of the absolute and relative sizes of S1 representations in cKO mice.
Figure 3: S1 size dictates the resolution and completeness of the body map.
Figure 4: The VPN thalamus was repatterned in cKO mice to match the reduced size and incomplete body map of S1.
Figure 5: Trigeminal hindbrain nuclei have normal somatotopic patterning in cKO mice.
Figure 6: Top-down plasticity repatterns the VPN through exaggerated apoptosis that is selective for VPN neurons representing body parts deleted from S1 in cKO mice.
Figure 7: Late differentiation of VPN TCA representations of PMBSF row A and the ALBSF in S1.
Figure 8: Altering the competitive balance among VPN TCAs rescues representations deleted from S1 body map in cKO mice.

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Acknowledgements

We thank B. Higgins and H. Gutierrez for technical assistance, J. Simon (Salk Institute MultiMedia Resources) for help making Adobe Illustrator schematics, Y. Dayn (Salk Institute Transgenic Core) for help producing the nestin-Pax6TG conditional transgenic mice, K. Jones (University of Colorado) for the Emx1-IRES-cre mice, M. Goulding (Salk Institute) for the ROSA26-GAP43-eGFP mice and members of the O'Leary lab for discussion. This work was supported by US National Institutes of Health grants R01 NS31558 and R01 MH086147 and the Vincent J. Coates Chair of Molecular Neurobiology (D.D.M.O.).

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Author notes

  1. Shen-Ju Chou & Ruth Ashery-Padan

    Present address: Present addresses: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan (S.-J.C.) and Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.A.-P).,

Authors and Affiliations

  1. Molecular Neurobiology Laboratory, The Salk Institute For Biological Studies, La Jolla, California, USA

    Andreas Zembrzycki, Shen-Ju Chou & Dennis D M O'Leary

  2. Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany

    Ruth Ashery-Padan & Anastassia Stoykova

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  1. Andreas Zembrzycki
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Contributions

A.Z. and D.D.M.O. designed the study, analyzed findings, prepared figures and wrote the paper. A.Z. performed the primary experiments. S.-J.C. and D.D.M.O. designed and generated the nestin-Pax6TG conditional transgenic mice. R.A.-P. and A.S. designed and generated the Pax6 cKO mice. All authors read and approved the final manuscript.

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Correspondence to Dennis D M O'Leary.

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Zembrzycki, A., Chou, SJ., Ashery-Padan, R. et al. Sensory cortex limits cortical maps and drives top-down plasticity in thalamocortical circuits. Nat Neurosci 16, 1060–1067 (2013). https://doi.org/10.1038/nn.3454

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