The dual role of the extracellular matrix in synaptic plasticity and homeostasis
Abstract
Recent studies have deepened our understanding of multiple mechanisms by which extracellular matrix (ECM) molecules regulate various aspects of synaptic plasticity and have strengthened a link between the ECM and learning and memory. New findings also support the view that the ECM is important for homeostatic processes, such as scaling of synaptic responses, metaplasticity and stabilization of synaptic connectivity. Activity-dependent modification of the ECM affects the formation of dendritic filopodia and the growth of dendritic spines. Thus, the ECM has a dual role as a promoter of structural and functional plasticity and as a degradable stabilizer of neural microcircuits. Both of these aspects are likely to be important for mental health.
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During development, the ECM and CSPGs regulate neuronal migration, axon outgrowth, synaptogenesis and synaptic maturation.
“During development, the ECM, and CSPGs in particular, regulate neuronal migration, axon outgrowth, synaptogenesis and synaptic maturation.23, 27, 28, 29, 30, 31”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [31]
PNNs control the lateral mobility of cell surface molecules including glutamatergic receptors, modulate L-type voltage-dependent calcium channels and voltage-gated potassium channels, and affect the local concentration of calcium ions.
“PNNs control the lateral mobility of cell surface molecules including glutamatergic receptors, thus regulating their availability on the postsynaptic membrane specialization, modulate L-type voltage-dependent calcium channels and voltage-gated potassium channels and affect the local concentration of calcium ions.30, 31, 87, 88”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [31]
Perineuronal nets (PNNs) contribute to the process of synaptogenesis.
“Although it is known for a few years that PNNs contribute to the process of synaptogenesis, it is not yet clear to which extent the different molecules are involved therein9,10,41.”
PNNs regulate synaptic functions and plasticity during development and adulthood.
“Long believed to be responsible primarily for structural support, PNNs have in recent years come to the forefront of neuroscience research as critical elements regulating synaptic functions and plasticity during development and adulthood (Beurdeley et al., 2012; Dityatev et al., 2010; Gogolla et al., 2009; Gundelfinger et al., 2010; Pizzorusso et al., 2002; Xue et al., 2014; Yamada and Jinno, 2013”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Dityatev et al., 2010
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Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins
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α3-Integrins are required for hippocampal long-term potentiation and working memoryPreprint
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Clustering transmembrane-agrin induces filopodia-like processes on axons and dendrites
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Cloning and sequencing of the cDNA encoding human neurotrypsin
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Human umbilical cord plasma proteins revitalize hippocampal function in aged mice
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Molecular signals of plasticity at the tetrapartite synapse
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Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology
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A role for microglia in synaptic plasticity?
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Integrins as receptor targets for neurological disorders
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“(Dityatev & Schachner, 2003; Gall et al., 2003; Gall & Lynch, 2004; Dityatev et al., 2010).”
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Shaping Synapses by the Neural Extracellular Matrix
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Decellularization for the retention of tissue niches
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Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology
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The Different Roles of Aggrecan Interaction Domains
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The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses.
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Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures
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Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration
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Brain extracellular matrix retains connectivity in neuronal networks
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Peripheral immune-derived matrix metalloproteinase promotes stress susceptibility
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“ECM degradation and remodeling is regulated by various enzymes, such as Matrix metalloproteinases (MMPs) 19,21 .”
Background
- Authors
- Dityatev, A., Schachner, M., & Sonderegger, P.
- Affiliations
- Italian Institute of Technology (IT)
- Rutgers, The State University of New Jersey (US)
- University of Zurich (CH)
- Corresponding author
- Dityatev, Alexander
- Venue
- Nature Reviews Neuroscience
- Published
- 2010-10-14
- Volume
- 11
- Issue
- 11
- Pages
- 735-746
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W1997218140
- Cited by
- 559
- References
- 121
- Citations by year
- 2026: 39 · 2025: 41 · 2024: 37 · 2023: 51 · 2022: 43 · 2021: 38 · 2020: 25 · 2019: 26 · 2018: 31 · 2017: 35 · 2016: 34 · 2015: 33 · 2014: 36 · 2013: 29 · 2012: 30
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- extracellular matrix, synaptic plasticity, synaptic homeostasis, proteolytic enzymes, metaplasticity, synaptic scaling, dendritic filopodia, learning and memory, neural microcircuits, mental health
- MeSH terms
- Animals, Extracellular Matrix, Homeostasis, Humans, Models, Biological, Neuronal Plasticity, Synapses, Calcium Channels, Signal Transduction, Receptors, N-Methyl-D-Aspartate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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