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Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex

  • Elena Maria Boggio
  • Erich M. Ehlert
  • Leonardo Lupori
  • Elizabeth B. Moloney
  • Fred De Winter
  • Craig W. Vander Kooi
  • Laura Baroncelli
  • Vasilis Mecollari
  • Bas Blits
  • James W. Fawcett
  • Joost Verhaagen
  • Tommaso PizzorussoEmail author
Article

Abstract

Perineuronal nets (PNNs) are condensed structures in the extracellular matrix that mainly surround GABA-ergic parvalbumin-positive interneurons in the adult brain. Previous studies revealed a parallel between PNN formation and the closure of the critical period. Moreover, ocular dominance plasticity is enhanced in response to PNN manipulations in adult animals. However, the mechanisms through which perineuronal nets modulate plasticity are still poorly understood. Recent work indicated that perineuronal nets may convey molecular signals by binding and storing proteins with important roles in cellular communication. Here we report that semaphorin3A (Sema3A), a chemorepulsive axon guidance cue known to bind to important perineuronal net components, is necessary to dampen ocular dominance plasticity in adult rats. First, we showed that the accumulation of Sema3A in PNNs in the visual cortex correlates with critical period closure, following the same time course of perineuronal nets maturation. Second, the accumulation of Sema3A in perineuronal nets was significantly reduced by rearing animals in the dark in the absence of any visual experience. Finally, we developed and characterized a tool to interfere with Sema3A signaling by means of AAV-mediated expression of receptor bodies, soluble proteins formed by the extracellular domain of the endogenous Sema3A receptor (neuropilin1) fused to a human IgG Fc fragment. By using this tool to antagonize Sema3A signaling in the adult rat visual cortex, we found that the specific inhibition of Sema3A promoted ocular dominance plasticity. Thus, Sema3A accumulates in perineuronal nets in an experience-dependent manner and its presence in the mature visual cortex inhibits plasticity.

Keywords

Visual cortex Critical period Chondroitin sulfate Inhibition 

Notes

Acknowledgments

The first four authors (marked with an asterisk) equally contributed to this study.

Funding Information

This work was supported by the EU 7th Framework program (FP7) Marie Curie actions (AxRegen) 2008–2012 to JV.

Compliance with Ethical Standards

All experiments were carried out in accordance with the European Communities Council Directive of November 24, 1986 (86/609/EEC) and were approved by the Italian Ministry of Health (authorization number 1152/2016-PR).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Elena Maria Boggio
    • 1
  • Erich M. Ehlert
    • 2
  • Leonardo Lupori
    • 3
  • Elizabeth B. Moloney
    • 2
  • Fred De Winter
    • 2
  • Craig W. Vander Kooi
    • 4
  • Laura Baroncelli
    • 1
    • 5
  • Vasilis Mecollari
    • 2
  • Bas Blits
    • 6
  • James W. Fawcett
    • 7
  • Joost Verhaagen
    • 2
    • 8
  • Tommaso Pizzorusso
    • 1
    • 3
    • 9
    Email author
  1. 1.Institute of NeuroscienceNational Research Council CNRPisaItaly
  2. 2.Laboratory for Regeneration of Sensorimotor SystemsNetherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and ScienceAmsterdamThe Netherlands
  3. 3.BIO@SNS labPisaItaly
  4. 4.Department of Molecular and Cellular Biochemistry and Center for Structural BiologyUniversity of KentuckyLexingtonUSA
  5. 5.Department of Developmental NeuroscienceIRCCS Stella Maris FoundationPisaItaly
  6. 6.UniQureAmsterdamThe Netherlands
  7. 7.John van Geest Centre for Brain RepairCambridgeUK
  8. 8.Center for Neurogenomics and Cognitive ResearchVrije Universiteit AmsterdamAmsterdamThe Netherlands
  9. 9.Department of Neuroscience, PsychologyDrug Research and Child Health NEUROFARBA University of FlorenceFlorenceItaly

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