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 Pizzorusso

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalMolecular Neurobiology
DOIs
Publication statusE-pub ahead of print - 31 Jan 2019

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ocular Dominance
Visual Cortex
Immunoglobulin Fc Fragments
Parvalbumins
Interneurons
gamma-Aminobutyric Acid
Cues
Extracellular Matrix
Carrier Proteins
Immunoglobulin G
Communication
Brain
Inhibition (Psychology)
Proteins
Critical Period (Psychology)

Keywords

  • Chondroitin sulfate
  • Critical period
  • Inhibition
  • Visual cortex

Cite this

Boggio, E. M., Ehlert, E. M., Lupori, L., Moloney, E. B., De Winter, F., Vander Kooi, C. W., ... Pizzorusso, T. (2019). Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex. Molecular Neurobiology, 1-11. https://doi.org/10.1007/s12035-019-1499-0
Boggio, Elena Maria ; Ehlert, Erich M. ; Lupori, Leonardo ; Moloney, Elizabeth B. ; De Winter, Fred ; Vander Kooi, Craig W. ; Baroncelli, Laura ; Mecollari, Vasilis ; Blits, Bas ; Fawcett, James W. ; Verhaagen, Joost ; Pizzorusso, Tommaso. / Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex. In: Molecular Neurobiology. 2019 ; pp. 1-11.
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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.",
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author = "Boggio, {Elena Maria} and Ehlert, {Erich M.} and Leonardo Lupori and Moloney, {Elizabeth B.} and {De Winter}, Fred and {Vander Kooi}, {Craig W.} and Laura Baroncelli and Vasilis Mecollari and Bas Blits and Fawcett, {James W.} and Joost Verhaagen and Tommaso Pizzorusso",
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Boggio, EM, Ehlert, EM, Lupori, L, Moloney, EB, De Winter, F, Vander Kooi, CW, Baroncelli, L, Mecollari, V, Blits, B, Fawcett, JW, Verhaagen, J & Pizzorusso, T 2019, 'Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex' Molecular Neurobiology, pp. 1-11. https://doi.org/10.1007/s12035-019-1499-0

Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex. / Boggio, Elena Maria; Ehlert, Erich M.; Lupori, Leonardo; Moloney, Elizabeth B.; De Winter, Fred; Vander Kooi, Craig W.; Baroncelli, Laura; Mecollari, Vasilis; Blits, Bas; Fawcett, James W.; Verhaagen, Joost; Pizzorusso, Tommaso.

In: Molecular Neurobiology, 31.01.2019, p. 1-11.

Research output: Contribution to JournalArticleAcademicpeer-review

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T1 - Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex

AU - Boggio, Elena Maria

AU - Ehlert, Erich M.

AU - Lupori, Leonardo

AU - Moloney, Elizabeth B.

AU - De Winter, Fred

AU - Vander Kooi, Craig W.

AU - Baroncelli, Laura

AU - Mecollari, Vasilis

AU - Blits, Bas

AU - Fawcett, James W.

AU - Verhaagen, Joost

AU - Pizzorusso, Tommaso

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AB - 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.

KW - Chondroitin sulfate

KW - Critical period

KW - Inhibition

KW - Visual cortex

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