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Diffuse perineuronal nets and modified pyramidal cells immunoreactive for glutamate and the GABAA receptor α1 subunit form a unique entity in rat cerebral cortex
Abstract
Perineuronal nets (PNs) consisting of polyanionic chondroitin sulfate proteoglycans (CSPG) and other extracellular matrix components create an exceptional microenvironment around certain types of neurons. In rat neocortex, three types of PNs can be distinguished after staining with Wisteria floribunda agglutinin (WFA) by their different morphological structure: lattice-like PNs associated with subpopulations of nonpyramidal neurons, weakly labeled PNs showing a pyramidal morphology, and diffuse PNs that possess a thick, strongly labeled matrix sheath located mainly in layer VIb above the white matter. The type of neuron surrounded by diffuse nets has not been described so far. This study is focused on the cytochemical and morphological characteristics of neurons associated with diffusely contoured PNs in rat parietal cortex using immunocytochemical staining, intracellular injection, and retrograde tracing methods. Cells surrounded by diffuse PNs were glutamate-immunoreactive in contrast to nonpyramidal, net-associated neurons that showed immunoreactivity for GABA, the calcium-binding protein parvalbumin and the potassium channel subunit Kv3.1b. Both groups of PN-ensheathed cells were mostly immunoreactive for the GABA(A) receptor alpha1 subunit. Lucifer Yellow-injected neurons surrounded by diffuse PNs displayed the morphological properties of modified pyramidal cells with intracortical main axons. Many neurons with diffuse PNs were retrogradely labeled over a long distance after Fluoro-Gold tracer injection in the parietal cortex, but remained unlabeled after intrathalamic injection. We conclude that neurons associated with diffuse PNs are a subpopulation of glutamatergic modified pyramidal cells that could act as excitatory long-range intracortically projecting neurons.
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“PNNs surround inhibitory fast spiking parvalbumin-positive GABAergic interneurons12–14, but are also associated with further subpopulations, for example excitatory pyramidal neurons in the cerebral cortex15,16.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [16]
In the citing paper
“Other cell types, including putative excitatory neurons also contain PNNs but they are less numerous compared to GABAergic-PNN expressing cells (Wegner et al., 2003).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Wegner et al., 2003
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Self-citationRitok, A., Kiss, P., Zaher, A., Wolf, E., Ducza, L., Bácskai, T., Matesz, C., & Gaál, B. (2022) · Scientific Reports · doi:10.1038/s41598-022-25692-3 · Cited by 3
Hussain, A., & Razak, K. A. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.05.026 · Cited by 4
Karthikeyan, S. S. (2017) · uO Research (University of Ottawa) · doi:10.20381/ruor-21084
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Metadata
- Authors
- Wegner, F., Härtig, W., Bringmann, A., Grosche, J., Wohlfarth, K., Zuschratter, W., & Brückner, G.
- Affiliations
- Leipzig University (DE)
- Leibniz Institute for Neurobiology (DE)
- Corresponding author
- Brückner, Gert
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 184
- Issue
- 2
- Pages
- 705-714
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2025692046
- Cited by
- 107
- References
- 74
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 1 · 2023: 2 · 2022: 10 · 2021: 8 · 2020: 3 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 3
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- glutamate immunoreactivity, GABA-A receptor alpha1 subunit, chondroitin sulfate proteoglycans, extracellular matrix, parietal cortex, glutamatergic neurons, retrograde tracing, parvalbumin, Wisteria floribunda agglutinin
- MeSH terms
- Animals, Cerebral Cortex, Extracellular Matrix, Female, Fluorescent Dyes, Immunohistochemistry, Isoquinolines, Male, Organ Culture Techniques, Chondroitin Sulfate Proteoglycans, Receptors, GABA-A, Stilbamidines, Rats, Wistar, Pyramidal Cells, Microscopy, Confocal, Glutamic Acid, Rats
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