Cerebellar plasticity and associative memories are controlled by perineuronal nets

Daniela Carulli; Robin Broersen; Fred de Winter; Elizabeth M. Muir; Maja Meškovic; Matthijs de Waal; Sharon de Vries; Henk Jan Boele; Cathrin B. Canto; Chris I. de Zeeuw; Joost Verhaagen

doi:10.1073/pnas.1916163117

Cerebellar plasticity and associative memories are controlled by perineuronal nets

Daniela Carulli^*, Robin Broersen, Fred de Winter, Elizabeth M. Muir, Maja Meškovic, Matthijs de Waal, Sharon de Vries, Henk Jan Boele, Cathrin B. Canto, Chris I. de Zeeuw, Joost Verhaagen

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.

Original language	English
Pages (from-to)	6855-6865
Number of pages	11
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	117
Issue number	12
DOIs	https://doi.org/10.1073/pnas.1916163117
Publication status	Published - 24 Mar 2020

Funding

ACKNOWLEDGMENTS. The work was supported by University of Turin, La Maratò de TV3, International Foundation for Research in Paraplegia, International Spinal Research Trust, the Netherlands Institute for Neuroscience, the Netherlands Organization for Scientific Research (Earth and Life Sciences), the Dutch Organization for Medical Sciences European Research Council-advanced, and European Research Council-Proof of Concept. We are grateful to Bas Koekkoek, Ilja IJpelaar, and Michiel ten Brinke (Erasmus Medical Center, Rotterdam, The Netherlands) for their help with the eyeblink conditioning paradigm, Willemijn Ranzijn (Netherlands Institute for Neuroscience, Amsterdam, The Netherlands) for her help with behavioral experiments and immunohistochemistry; and Barbara Hobo, Cynthia Geelen, and Anna Court (Netherlands Institute for Neuroscience, Amsterdam, The Netherlands) for their excellent technical support.

Funders	Funder number
Dutch Organization for Medical Sciences European Research Council-advanced
European Research Council-Proof of Concept
Netherlands Institute for Neuroscience
International Spinal Research Trust
International Foundation for Research in Paraplegia
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Università degli Studi di Torino

Keywords

Cerebellum
Eyeblink conditioning
Learning
Perineuronal net
Plasticity

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10.1073/pnas.1916163117

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Carulli, D., Broersen, R., de Winter, F., Muir, E. M., Meškovic, M., de Waal, M., de Vries, S., Boele, H. J., Canto, C. B., de Zeeuw, C. I., & Verhaagen, J. (2020). Cerebellar plasticity and associative memories are controlled by perineuronal nets. Proceedings of the National Academy of Sciences of the United States of America, 117(12), 6855-6865. https://doi.org/10.1073/pnas.1916163117

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title = "Cerebellar plasticity and associative memories are controlled by perineuronal nets",

abstract = "Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.",

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Carulli, D, Broersen, R, de Winter, F, Muir, EM, Meškovic, M, de Waal, M, de Vries, S, Boele, HJ, Canto, CB, de Zeeuw, CI & Verhaagen, J 2020, 'Cerebellar plasticity and associative memories are controlled by perineuronal nets', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 12, pp. 6855-6865. https://doi.org/10.1073/pnas.1916163117

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AU - Muir, Elizabeth M.

AU - Meškovic, Maja

AU - de Waal, Matthijs

AU - de Vries, Sharon

AU - Boele, Henk Jan

AU - Canto, Cathrin B.

AU - de Zeeuw, Chris I.

AU - Verhaagen, Joost

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N2 - Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.

AB - Perineuronal nets (PNNs) are assemblies of extracellular matrix molecules, which surround the cell body and dendrites of many types of neuron and regulate neural plasticity. PNNs are prominently expressed around neurons of the deep cerebellar nuclei (DCN), but their role in adult cerebellar plasticity and behavior is far from clear. Here we show that PNNs in the mouse DCN are diminished during eyeblink conditioning (EBC), a form of associative motor learning that depends on DCN plasticity. When memories are fully acquired, PNNs are restored. Enzymatic digestion of PNNs in the DCN improves EBC learning, but intact PNNs are necessary for memory retention. At the structural level, PNN removal induces significant synaptic rearrangements in vivo, resulting in increased inhibition of DCN baseline activity in awake behaving mice. Together, these results demonstrate that PNNs are critical players in the regulation of cerebellar circuitry and function.

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Cerebellar plasticity and associative memories are controlled by perineuronal nets

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Keywords

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