Cerebellar plasticity and associative memories are controlled by perineuronal nets
Open Access
- 9 March 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 117 (12), 6855-6865
- https://doi.org/10.1073/pnas.1916163117
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.Keywords
Funding Information
- University of Turin (n.a.)
- Fundació la Marató de TV3 (TV3-201736-30-31)
- International Spinal Research Trust (TR1004)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (102013)
- ZonMw (102245)
- European Research Council Advanced Grant (103120)
- ERC-POC (107568)
- Netherlands Institute for Neuroscience (n.a.)
This publication has 81 references indexed in Scilit:
- Otx2 Binding to Perineuronal Nets Persistently Regulates Plasticity in the Mature Visual CortexJournal of Neuroscience, 2012
- Lentiviral vectors express chondroitinase ABC in cortical projections and promote sprouting of injured corticospinal axonsJournal of Neuroscience Methods, 2011
- Experience-Dependent Plasticity and Modulation of Growth Regulatory Molecules at Central SynapsesPLOS ONE, 2011
- Extracellular Matrix Plasticity and GABAergic Inhibition of Prefrontal Cortex Pyramidal Cells Facilitates Relapse to Heroin SeekingNeuropsychopharmacology, 2010
- Animals lacking link protein have attenuated perineuronal nets and persistent plasticityBrain, 2010
- Modification of N-glycosylation sites allows secretion of bacterial chondroitinase ABC from mammalian cellsJournal of Biotechnology, 2010
- Synaptic mitochondria in synaptic transmission and organization of vesicle pools in health and diseaseFrontiers in Synaptic Neuroscience, 2010
- Ca Currents Activated by Spontaneous Firing and Synaptic Disinhibition in Neurons of the Cerebellar NucleiJournal of Neuroscience, 2009
- Nothing can be coincidence: synaptic inhibition and plasticity in the cerebellar nucleiTrends in Neurosciences, 2009
- Lock-and-Key Mechanisms of Cerebellar Memory Recall Based on Rebound CurrentsJournal of Neurophysiology, 2008