The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function
Abstract
Perineuronal nets (PNNs) are extracellular matrix (ECM) chondroitin sulfate proteoglycan (CSPG)-containing structures that surround the soma and dendrites of various mammalian neuronal cell types. PNNs appear during development around the time that the critical periods for developmental plasticity end and are important for both their onset and closure. A similar structure - the perinodal ECM - surrounds the axonal nodes of Ranvier and appears as myelination is completed, acting as an ion-diffusion barrier that affects axonal conduction speed. Recent work has revealed the importance of PNNs in controlling plasticity in the CNS. Digestion, blocking or removal of PNNs influences functional recovery after a variety of CNS lesions. PNNs have further been shown to be involved in the regulation of memory and have been implicated in a number of psychiatric disorders.
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PNNs are reticular CSPG-containing ECM structures surrounding the soma and proximal dendrites of a subpopulation of CNS neurons and are important for controlling neuroplasticity.
“PNNs are reticular CSPG-containing ECM structures surrounding the soma and proximal dendrites of a subpopulation of CNS neurons and important for controlling neuroplasticity [1, 13].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [1]
The lectican family of CSPGs (aggrecan, brevican, neurocan, and versican) are found within PNNs.
“The lectican family of CSPGs (also called aggrecan-family CSPGs) are found within PNNs, including aggrecan, brevican, neurocan, and versican [1].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [1]
PNNs are now being considered as a target for the treatment of impaired memory.
“PNNs are now being considered as a target for the treatment of impaired memory.”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [1]
PNNs exclusively enwrap the soma and most proximal segments of dendrites.
“It has to be taken also into account that PNNs exclusively enwrap the soma and most proximal segments of dendrites (Celio et al., 1998;Fawcett et al., 2019)”
From Perineuronal Nets Regulate the Inhibitory Perisomatic Input onto Parvalbumin Interneurons and γ Activity in the Prefrontal Cortex (2020) · cites this paper as Fawcett et al., 2019
Perineuronal nets form preferentially around fast-spiking parvalbumin-positive GABAergic interneurons throughout the brain during closure of the critical period of plasticity, locking proximal synapses in place and providing synaptic stability.
“PNNs form preferentially around fast-spiking parvalbumin (PV)+ GABAergic interneurons throughout the brain during the closure of the critical period of plasticity, effectively “locking” proximal synapses in place and providing synaptic stability [21] soon after synaptic pruning is completed by developmental microglia [22].”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [21]
Contrasting effects of PNN ablation on certain memory tasks and measures of plasticity suggest this is not the case for all types of memory, but differences may be partly attributable to the PNN ablation method used.
“Although contrasting effects of PNN ablation on certain (specifically object recognition) memory tasks and measures of plasticity suggest this is not the case for all types of memory [21, 29, 87], such differences may also be at least partly attributable to the PNN ablation method utilized (e.g. enzymatic digestion vs genetic deletion of PNN components) which can produce differential effects on”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [21]
CSPGs can be preferentially incorporated into conventional PNNs depending on side-chain sulphation.
“Depending on side chain sulphation pattern, CSPGs can also be preferentially incorporated into conventional PNNs”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Fawcett et al., 2019
PNNs stabilize neuronal circuitry and inhibit plasticity.
“stabilizing the neuronal circuitry and inhibiting plasticity (Wang and Fawcett, 2012; Fawcett et al. , 2019).”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Fawcett et al. , 2019
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- Authors
- Fawcett, J. W., Oohashi, T., & Pizzorusso, T.
- Affiliations
- Czech Academy of Sciences (CZ)
- Okayama University (JP)
- Neuroscience Institute (IT)
- Corresponding author
- Fawcett, James W.
- Venue
- Nature Reviews Neuroscience
- Published
- 2019-07-01
- Volume
- 20
- Issue
- 8
- Pages
- 451-465
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2955918581
- Semantic Scholar
- e14cf9b70c48b98946ffcfb2145a00841a74cb04
- Cited by
- 589
- References
- 228
- Citations by year
- 2026: 85 · 2025: 114 · 2024: 89 · 2023: 83 · 2022: 74 · 2021: 79 · 2020: 54 · 2019: 9 · 2018: 1
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Scuola Normale Superiore di Pisa (submittedVersion)
- Funders
- Medical Research Council (MR/R004463/1, MR/R004544/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- perineuronal nets, chondroitin sulfate proteoglycans, extracellular matrix, critical period, developmental plasticity, CNS plasticity, memory regulation, mental illness, nodes of Ranvier, myelination
- MeSH terms
- Animals, Mental Disorders, Central Nervous System Diseases, Extracellular Matrix, Humans, Memory, Models, Neurological, Neuronal Plasticity, Neurons
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