Cerebellar plasticity and associative memories are controlled by perineuronal nets

TY - JOUR

T1 - Cerebellar plasticity and associative memories are controlled by perineuronal nets

AU - Carulli, Daniela

AU - Broersen, Robin

AU - de Winter, Fred

AU - Muir, Elizabeth M

AU - Mešković, 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

N1 - Copyright © 2020 the Author(s). Published by PNAS.

PY - 2020/3/9

Y1 - 2020/3/9

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.

U2 - 10.1073/pnas.1916163117

DO - 10.1073/pnas.1916163117

M3 - Article

C2 - 32152108

VL - 117

SP - 6855

EP - 6865

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

ER -