%0 Journal Article
%A Singh, Jeet Bahadur
%A Perelló-Amorós, Bartomeu
%A Schneeberg, Jenny
%A Mirzapourdelavar, Hadi
%A Seidenbecher, Constanze I
%A Fejtová, Anna
%A Dityatev, Alexander
%A Frischknecht, Renato
%T Activity-dependent extracellular proteolytic cascade cleaves the ECM component brevican to promote structural plasticity.
%J EMBO reports
%V 27
%N 1
%@ 1469-221X
%C [London]
%I Nature Publishing Group UK
%M DZNE-2026-00063
%P 163 - 185
%D 2026
%X 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.
%K Animals
%K Brevican: metabolism
%K Extracellular Matrix: metabolism
%K Rats
%K Neuronal Plasticity
%K Long-Term Potentiation
%K Proteolysis
%K Astrocytes: metabolism
%K Hippocampus: metabolism
%K Hippocampus: physiology
%K Male
%K Synapses: metabolism
%K Receptors, N-Methyl-D-Aspartate: metabolism
%K Neurons: metabolism
%K ADAMTS (Other)
%K Aggrecan (Other)
%K Dendritic Spines (Other)
%K Perineuronal Nets (Other)
%K Proprotein Convertase (Other)
%K Brevican (NLM Chemicals)
%K Receptors, N-Methyl-D-Aspartate (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41261283
%R 10.1038/s44319-025-00644-w
%U https://pub.dzne.de/record/283184