Activity-dependent extracellular proteolytic cascade cleaves the ECM component brevican to promote structural plasticity

Singh JB, Perelló Amorós B, Schneeberg J, Mirzapourdelavar H, Seidenbecher CI, Fejtová A, Dityatev A, Frischknecht R (2025)

Publication Type: Journal article

Publication year: 2025

Journal

EMBO Reports EMBO Press

DOI: 10.1038/s44319-025-00644-w

Abstract

The brain’s perineuronal extracellular matrix (ECM) is a crucial factor in maintaining the stability of mature brain circuitry. However, how activity-induced synaptic plasticity is achieved in the adult brain with a dense ECM is unclear. We hypothesized that neuronal activity induces cleavage of ECM, creating conditions for synaptic rearrangements. To test this hypothesis, we investigated neuronal activity-dependent proteolytic cleavage of brevican, a prototypical ECM proteoglycan, and the importance of this process for functional and structural synaptic plasticity in the rat hippocampus ex vivo. Our findings reveal that chemical long-term potentiation (cLTP) triggers rapid brevican cleavage in perisynaptic regions through the activation of an extracellular proteolytic cascade involving proprotein convertases and ADAMTS-4 and ADAMTS-5. This process requires NMDA receptor activation and involves astrocytes. Interfering with cLTP-induced brevican cleavage prevents the formation of new dendritic protrusions in CA1 but does not impact LTP induction by theta-burst stimulation of CA3-CA1 synapses. Our data reveal a mechanism of activity-dependent ECM remodeling and suggest that ECM degradation is essential for structural synaptic plasticity.

Authors with CRIS profile

Bartomeu Perelló Amorós Lehrstuhl für Tierphysiologie Anna Fejtová Professur für Molekulare Psychiatrie Renato Frischknecht Lehrstuhl für Tierphysiologie

Involved external institutions

Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) DE Germany (DE) Leibniz-Institut für Neurobiologie (LIN) DE Germany (DE)

How to cite

APA:

Singh, J.B., Perelló Amorós, B., Schneeberg, J., Mirzapourdelavar, H., Seidenbecher, C.I., Fejtová, A.,... Frischknecht, R. (2025). Activity-dependent extracellular proteolytic cascade cleaves the ECM component brevican to promote structural plasticity. EMBO Reports. https://doi.org/10.1038/s44319-025-00644-w

MLA:

Singh, Jeet Bahadur, et al. "Activity-dependent extracellular proteolytic cascade cleaves the ECM component brevican to promote structural plasticity." EMBO Reports (2025).

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