Increased Excitability and Reduced Excitatory Synaptic Input Into Fast-Spiking CA2 Interneurons After Enzymatic Attenuation of Extracellular Matrix
Open accessAbstract
The neural extracellular matrix (ECM) is enriched with hyaluronic acid, chondroitin sulfate proteoglycans (CSPGs), and the glycoprotein tenascin-R, which play important roles in synaptic plasticity, as shown by studies of the CA1 region of the hippocampus. However, ECM molecules are strongly expressed in the CA2 region, which harbors a high number of fast-spiking interneurons (FSIs) surrounded by a particularly condensed form of ECM, perineuronal nets. Despite this intriguing peculiarity, the functional role of ECM in the CA2 region is mostly unknown. Here, we investigate the acute and delayed effects of chondroitinase ABC (ChABC), an enzyme that digests chondroitin sulfate side chains of CSPGs and greatly attenuates neural ECM, on neuronal excitability and excitatory transmission in the CA2 region. Whole-cell patch clamp recordings of CA2 pyramidal cells (PCs) and FSIs in hippocampal slices revealed that seven days after injection of ChABC into the CA2 region in vivo, there are alterations in excitability of FSIs and PCs. FSIs generated action potentials with larger amplitudes and longer durations in response to less depolarizing currents compared to controls. PCs were excited at less depolarized membrane potentials, resulted in lower latency of spike generation. The frequency of excitatory postsynaptic currents in FSIs was selectively reduced, while the frequency of inhibitory postsynaptic currents was selectively increased. Acute treatment of hippocampal slices with ChABC did not result in any of these effects. This increase in excitability and changes in synaptic inputs to FSIs after attenuation of ECM suggests a crucial role for perineuronal nets associated with FSIs in regulation of synaptic and electrical properties of these cells.
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The WFA signal in CA2 is PNN-specific.
“This agrees with recent studies that emphasize that the WFA signal in CA2 is PNN-specific37,38.”
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 [38]
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- Authors
- Hayani, H., Song, I., & Dityatev, A.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Dityatev, Alexander
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-05-30
- Volume
- 12
- Pages
- 149-149
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC5988902
- OpenAlex
- W2805407131
- Cited by
- 84
- References
- 70
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 10 · 2023: 9 · 2022: 18 · 2021: 11 · 2020: 13 · 2019: 9 · 2018: 1
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DZNE Pub (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (DI 702/8-1 and B14 in SFB779)
- 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
- extracellular matrix, perineuronal nets, fast-spiking interneurons, chondroitinase ABC, chondroitin sulfate proteoglycans, neuronal excitability, excitatory synaptic input, pyramidal neurons, excitatory postsynaptic currents, inhibitory postsynaptic currents, hyaluronic acid, tenascin-R
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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