Structural maturation of cortical perineuronal nets and their perforating synapses revealed by superresolution imaging
Open accessAbstract
Significance: Particular inhibitory neurons containing parvalbumin (PV) play a critical role in determining the time course by which experience shapes developing brain circuits. Embedded deep within cortical gray matter, extracellular matrices enwrapping PV-positive (PV+) cells have remained difficult to study partly due to the small length scale on which they are organized. To overcome such challenges, we used a superresolution fluorescence imaging approach to visualize these perineuronal nets (PNNs), a specialized form of the extracellular matrix critical for maintaining mature PV+ neuron function and their synaptic inputs. We quantified changes that define PNN structure and identified specific synaptic defects in a mouse model lacking MeCP2 , the causative gene for Rett syndrome, a regressive neurodevelopmental disorder.
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PNN has an indirect role over principal neurons via regulating synaptic plasticity and dendritic arborization of the interneuron.
“PNN has an indirect role over principal neurons via regulating synaptic plasticity (Sigal et al., 2019) and dendritic arborization (Stolp et al., 2019) of the interneuron.”
From Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis (2020) · cites this paper as Sigal et al., 2019
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Cites
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“We envision that the volumetric superresolution imaging platform reported here, which allows molecular imaging with nanometerscale resolution across large tissue volumes, can be applied to track the pathogenesis of a variety of mental illnesses linked to disruptions in neuronal networks and the extracellular matrix (5…”
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“Defects in PV+ circuits, gamma oscillations, and critical period timing have been implicated in numerous mental disorders (5, 6).”
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“The condensed PNN is thought to act as a molecular brake on synaptic plasticity as critical periods close (10, 11), and cleavage of PNN components can partially reopen plasticity in adulthood (12, 13).”
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“PNN has an indirect role over principal neurons via regulating synaptic plasticity (Sigal et al., 2019) and dendritic arborization (Stolp et al., 2019) of the interneuron.”
Background
- Authors
- Sigal, Y. M., Bae, H., Bogart, L. J., Hensch, T. K., & Zhuang, X.
- Affiliations
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Boston Children's Hospital (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-03-19
- Volume
- 116
- Issue
- 14
- Pages
- 7071-7076
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6452715
- OpenAlex
- W2922660066
- Cited by
- 118
- References
- 11
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 13 · 2023: 15 · 2022: 21 · 2021: 20 · 2020: 16 · 2019: 6
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (P50MH094271)
- Howard Hughes Medical Institute (HHMI)
- HHS | NIH | National Institute of General Medical Sciences (R35GM122487)
- 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
- perineuronal nets, parvalbumin interneurons, extracellular matrix, cortical development, MeCP2, Rett syndrome, inhibitory interneurons, synaptic defects, super-resolution imaging
- MeSH terms
- Animals, Male, Nerve Net, Neuronal Plasticity, Synapses, Visual Cortex, Rett Syndrome, Synaptotagmin II, Mice, Methyl-CpG-Binding Protein 2
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