The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Persistent cortical plasticity by upregulation of chondroitin 6-sulfation
Abstract
Cortical plasticity is most evident during a critical period in early life, but the mechanisms that restrict plasticity after the critical period are poorly understood. We found that a developmental increase in the 4-sulfation/6-sulfation (4S/6S) ratio of chondroitin sulfate proteoglycans (CSPGs), which are components of the brain extracellular matrix, leads to the termination of the critical period for ocular dominance plasticity in the mouse visual cortex. Condensation of CSPGs into perineuronal nets that enwrapped synaptic contacts on parvalbumin-expressing interneurons was prevented by cell-autonomous overexpression of chondroitin 6-sulfation, which maintains a low 4S/6S ratio. Furthermore, the increase in the 4S/6S ratio was required for the accumulation of Otx2, a homeoprotein that activates the development of parvalbumin-expressing interneurons, and for functional maturation of the electrophysiological properties of these cells. Our results indicate that the critical period for cortical plasticity is regulated by the 4S/6S ratio of CSPGs, which determines the maturation of parvalbumin-expressing interneurons.
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In the citing paper
“As a result, transgenic mice overexpressing C6ST--1 retain a juvenile level of ocular dominance plasticity even in adulthood (Miyata et al., 2012).”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Miyata et al., 2012
In the citing paper
“Overall then, there is a substantial increase in the 4--sulfation/6-sulfation (C4S/C6S) ratio during brain development (Kitagawa et al., 1997;Miyata et al., 2012).”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Miyata et al., 2012
In the citing paper
“Specifically, 6--O--sulfation is dominant in the juvenile brain to produce C6S, which is more permissive (Lin et al., 2011;Miyata et al., 2012)”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Miyata et al., 2012
In the citing paper
“While chondroitin 4-sulphates (C4S) are inhibitory [5], chondroitin 6-sulphates (C6S) are more permissive to plasticity and regeneration [173, 174], and the balance between C6S and C4S regulates neuroplasticity.”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [173]
In the citing paper
“The relative abundance of CS isomers incorporated into the CS-GAG chains has been linked to key biological functions within the brain including charged molecule diffusion (0S-CS (Nicholson & Hrabětová 2017)), neurocircuit plasticity (4S-CS and 6S-CS (Miyata et al. 2012; Yang et al. 2021)), glial scarring (4S6S-CS (Brown et al. 2012)), and neurite outgrowth (2S6S-CS (Shida et al. 2019; Clement et a”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Miyata et al. 2012
In the citing paper
“Recent work suggests that microgliosis represents a potential mechanism driving PNN loss in models of neurodegeneration (Miyata et al. 2012; Miyata & Kitagawa 2016; Crapser et al. 2021)”
From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Miyata et al. 2012
In the citing paper
“Second, PNN disruption prevents the persistent uptake of Otx2 homeoprotein into the enwrapped PV-cells required for their maintenance (27, 40, 41) (Fig. S3).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [40]
In the citing paper
“Compromised PNNs prevent the persistent uptake of Otx2 homeoprotein into the enwrapped PV-cells needed for their maturation (including PNN maintenance itself) (27, 40, 41).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [40]
In the citing paper
“This is further supported by the demonstration that the knock-out of specific sulfotranferases that modify the PNN structure interferes with Otx2 internalization and CP closure (Miyata et al., 2012)”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Miyata et al., 2012
In the citing paper
“The model also stipulates that early sensory experience (sensory input) initiates expression of Otx2 binding sites on nascent PNNs (Beurdeley et al., 2012; Miyata et al., 2012), facilitating Otx2 import and opening a period of plasticity.”
From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Miyata et al., 2012
In the citing paper
“where they form a reticular dendrosomatic structure around largely parvalbumin-expressing interneurons”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Miyata et al., 2012
In the citing paper
“Chondroitin-4-sulfation (CS-4) and chondroitin-6 sulfation (CS-6) are the two most common sulfation patterns in the brain, with several variations depending on the position of the sulfation on the CS chains43, 44”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [43]
In the citing paper
“Numbers of CS chains and their patterns of sulfation fundamentally affect their functions, such as their ability to interact with other molecules including growth factors and cytokines.43”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [43]
In the citing paper
“Fourth, disruption of PNNs can alter the resting membrane potential of PV neurons (Miyata et al, 2012) and decrease the amplitudes of both inhibitory (Liu et al, 2013) and excitatory (Pyka et al, 2011) postsynaptic currents.”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Miyata et al, 2012
In the citing paper
“Several studies suggest that ECM components, including PNNs, are critical regulators of synaptic plasticity (Do et al, 2015;Miyata et al, 2012;Morishita et al, 2015).”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Miyata et al, 2012
In the citing paper
“For example, altered sulfation of N-acetylgalactosamine (GalNAc, a major disaccharide found in CSPGs) results in greatly reduced WFA labeling (Miyata et al, 2012).”
From Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia (2016) · cites this paper as Miyata et al, 2012
In the citing paper
“Interestingly, it has been recently shown that a developmental increase in the 4-sulfation/6-sulfation (4S/6S) ratio of CSPGs has a role in the closure of the critical period for ocular dominance plasticity in the mouse visual cortex, and condensation of CSPGs into PNNs is prevented by cell-autonomous overexpression of chondroitin 6-sulfation, which maintains a low 4S/6S ratio (Miyata et al., 2012”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Miyata et al., 2012
In the citing paper
“Indeed, the maturation and phenotypic maintenance of PVI require incorporation of a non-cell autonomous homeobox protein, Otx2, through its affinity with PNN (Beurdeley et al., 2012; Miyata et al., 2012).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Miyata et al., 2012
In the citing paper
“Given the pivotal role of PVI, PNN, and myelin in regulating brain plasticity dynamics and active epochs (McGee et al., 2005; Miyata et al., 2012; Morishita and Hensch, 2008), the dysregulation of this “hub” could yield the slow emergence of clinical symptoms by altering the timing of key windows of critical period of brain plasticity (Morishita et al., 2010, abstract Neuroscience Meeting, 62.30).”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Miyata et al., 2012
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Metadata
- Authors
- Miyata, S., Komatsu, Y., Yoshimura, Y., Taya, C., & Kitagawa, H.
- Affiliations
- Kobe Pharmaceutical University (JP)
- Research Institute of Environmental Medicine, Nagoya University (JP)
- National Institutes of Natural Sciences (JP)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Corresponding author
- Kitagawa, Hiroshi
- Venue
- Nature Neuroscience
- Published
- 2012-01-15
- Volume
- 15
- Issue
- 3
- Pages
- 414-422
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2078474557
- Cited by
- 365
- References
- 49
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 23 · 2023: 22 · 2022: 23 · 2021: 38 · 2020: 36 · 2019: 25 · 2018: 25 · 2017: 26 · 2016: 18 · 2015: 28 · 2014: 28 · 2013: 26 · 2012: 6
- FWCI
- 13.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University Research Committee, Emory University
- Japan Society for the Promotion of Science (21390025, 23110003)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- chondroitin sulfate proteoglycans, ocular dominance plasticity, critical period, visual cortex, parvalbumin interneurons, perineuronal nets, extracellular matrix, Otx2, interneuron maturation, cortical plasticity
- MeSH terms
- Carbohydrate Sulfotransferases, Action Potentials, Age Factors, Amphetamines, Animals, Animals, Newborn, Astrocytes, Bacterial Proteins, Cells, Cultured, Chlorocebus aethiops, Chondroitin Sulfates, Humans, Functional Laterality, Luminescent Proteins, Mice, Transgenic, Nerve Tissue Proteins, Neuronal Plasticity, Parvalbumins, Chondroitin Sulfate Proteoglycans, Sensory Deprivation, Time Factors, Visual Cortex, Visual Pathways, Sulfotransferases, Up-Regulation, Electroporation, Patch-Clamp Techniques, Gene Expression Regulation, Developmental, Receptors, N-Acetylglucosamine, Plant Lectins, Vesicular Glutamate Transport Protein 2, Mice, Otx Transcription Factors, Aggrecans, In Vitro Techniques
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