Seizure-like activity in hyaluronidase-treated dissociated hippocampal cultures
Open accessAbstract
The extracellular matrix (ECM) plays an important role in use-dependent synaptic plasticity. Hyaluronic acid (HA) is the backbone of the neural ECM, which has been shown to modulate α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptor mobility, paired-pulse depression, L-type voltage-dependent Ca(2+) channel (L-VDCC) activity, long-term potentiation and contextual fear conditioning. To investigate the role of HA in the development of spontaneous neuronal network activity, we used microelectrode array recording and Ca(2+) imaging in hippocampal cultures enzymatically treated with hyaluronidase. Our findings revealed an appearance of epileptiform activity 9 days after hyaluronidase treatment. The treatment transformed the normal network firing bursts and Ca(2+) oscillations into long-lasting "superbursts" and "superoscillations" with durations of 11-100 s. The changes in Ca(2+) transients in hyaluronidase-treated neurons were more prominent then in astrocytes and preceded changes in electrical activity. The Ca(2+) superoscillations could be suppressed by applying the L-VDCC blocker diltiazem, whereas the neuronal firing superbursts could be additionally suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione as an antagonist of AMPA/kainate receptors. These results suggest that changes in the expression of HA can be epileptogenic and that hyaluronidase treatment in vitro provides a robust model for the dissection of the underlying mechanisms.
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Hippocampal neuronal cultures treated with hyaluronidase developed epileptiform activity due to superbursts.
“Furthermore, hippocampal neuronal cultures treated with hyaluronidase developed an epileptiform activity due to the occurrence of superbursts58.”
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 [58]
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- Authors
- Vedunova, M., Sakharnova, T., Mitroshina, E., Perminova, M., Pimashkin, A., Zakharov, Y., Dityatev, A., & Mukhina, I.
- Affiliations
- N. I. Lobachevsky State University of Nizhny Novgorod (RU)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Dityatev, Alexander
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 149-149
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3770920
- OpenAlex
- W2117184636
- Cited by
- 107
- References
- 28
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 13 · 2019: 16 · 2018: 11 · 2017: 5 · 2016: 9 · 2015: 12 · 2014: 6 · 2013: 1
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- 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)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- hyaluronidase, hyaluronic acid, extracellular matrix, epileptiform activity, hippocampal cultures, L-type voltage-dependent calcium channels, non-NMDA receptors, diltiazem, spontaneous network activity, astrocytes, epileptogenesis
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