The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.
Primary Hippocampal Neurons, Which Lack Four Crucial Extracellular Matrix Molecules, Display Abnormalities of Synaptic Structure and Function and Severe Deficits in Perineuronal Net Formation
Open accessAbstract
The extracellular matrix (ECM) of the brain plays crucial roles during the development, maturation, and regeneration of the CNS. In a subpopulation of neurons, the ECM condenses to superstructures called perineuronal nets (PNNs) that surround synapses. Camillo Golgi described PNNs a century ago, yet their biological functions remain elusive. Here, we studied a mouse mutant that lacks four ECM components highly enriched in the developing brain: the glycoproteins tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans brevican and neurocan. Primary embryonic hippocampal neurons and astrocytes were cultivated using a cell insert system that allows for co-culture of distinct cell populations in the absence of direct membrane contacts. The wild-type and knock-out cells were combined in the four possible permutations. Using this approach, neurons cultivated in the presence of mutant astrocytes displayed a transient increase of synapses after 2 weeks. However, after a period of 3 weeks or longer, synapse formation and stabilization were compromised when either neuron or astrocyte cell populations or both were of mutant origin. The development of PNN structures was observed, but their size was substantially reduced on knock-out neurons. The synaptic activity of both wild-type and knock-out neurons was monitored using whole-cell patch clamping. The salient observation was a reduced frequency of IPSCs and EPSCs, whereas the amplitudes were not modified. Remarkably, the knock-out neuron phenotypes could not be rescued by wild-type astrocytes. We conclude that the elimination of four ECM genes compromises neuronal function.
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In the citing paper
“This may be due in part to the degradation of the PNNs in which synapses are embedded, as the genetic ablation of one or more PNN structural components and consequent loss of neuronal PNN integrity can induce the loss of synapses [28, 80] and impaired synaptic colocalization/expression of neurotransmitter receptor subunits [29], potentially manifesting as deficits in synaptic plasticity (e.g. LTP)”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [80]
In the citing paper
“PNNs are autonomously constructed by neurons (Miyata et al. , 2005; Geissler et al. , 2013; Fowke et al. , 2017)”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Geissler et al. , 2013
In the citing paper
“In a previous study our laboratory investigated hippocampal neurons of the quadruple knockout mouse in vitro and found diminished PNNs and an altered expression of synaptic proteins that were accompanied by a decreased frequency of mEPSCs and mIPSCs after 14 and 21 DIV29.”
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 [29]
In the citing paper
“The results found for the in vivo PNN formation fit perfectly with the in vitro findings29, both demonstrating a diminished PNN formation in the postnatal quadruple knockout mouse.”
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 [29]
In the citing paper
“The loss of TnC, TnR, brevican and neurocan resulted in a significant increase of synaptic density within 14 DIV that transited to a decremented synapse number after 21 DIV.”
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 [29]
In the citing paper
“Neurons coated with PNNs were characterized by an attenuated synapse number after both 14 and 21 DIV29.”
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 [29]
In the citing paper
“In this model hippocampal neurons lacking neurocan, brevican, TN-R and TN-C display rudimentary PNNs and reduced synapse number, suggesting that PNNs are important for synapse formation/stabilization (Geissler et al., 2013).”
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 Geissler et al., 2013
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Metadata
- Authors
- Geissler, M., Gottschling, C., Aguado, A., Rauch, U., Wetzel, C. H., Hatt, H., & Faissner, A.
- Affiliations
- Ruhr University Bochum (DE)
- Lund University (SE)
- University of Regensburg (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-05-01
- Volume
- 33
- Issue
- 18
- Pages
- 7742-7755
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6618965
- OpenAlex
- W2012448906
- Cited by
- 140
- References
- 86
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 13 · 2022: 12 · 2021: 15 · 2020: 18 · 2019: 10 · 2018: 11 · 2017: 16 · 2016: 7 · 2015: 8 · 2014: 11 · 2013: 3
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- perineuronal nets, extracellular matrix, hippocampal neurons, astrocytes, tenascin-C, tenascin-R, brevican, neurocan, chondroitin sulfate proteoglycans, synaptogenesis, synapse stabilization, inhibitory postsynaptic currents, excitatory postsynaptic currents, co-culture, embryonic neurons
- MeSH terms
- Animals, Astrocytes, Cell Count, Cells, Cultured, Embryo, Mammalian, Female, Hippocampus, Male, Mice, Inbred C57BL, Nerve Net, Neurons, Synapses, Extracellular Matrix Proteins, Mice, Knockout, Gene Expression Regulation, Developmental, Coculture Techniques, Tenascin, Excitatory Postsynaptic Potentials, Mice, Inhibitory Postsynaptic Potentials, Neurocan, Brevican
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