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000283184 1001_ $$00000-0003-1738-2060$$aSingh, Jeet Bahadur$$b0
000283184 245__ $$aActivity-dependent extracellular proteolytic cascade cleaves the ECM component brevican to promote structural plasticity.
000283184 260__ $$a[London]$$bNature Publishing Group UK$$c2026
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000283184 520__ $$aThe 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.
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000283184 650_7 $$2Other$$aADAMTS
000283184 650_7 $$2Other$$aAggrecan
000283184 650_7 $$2Other$$aDendritic Spines
000283184 650_7 $$2Other$$aPerineuronal Nets
000283184 650_7 $$2Other$$aProprotein Convertase
000283184 650_7 $$2NLM Chemicals$$aBrevican
000283184 650_7 $$2NLM Chemicals$$aReceptors, N-Methyl-D-Aspartate
000283184 650_2 $$2MeSH$$aAnimals
000283184 650_2 $$2MeSH$$aBrevican: metabolism
000283184 650_2 $$2MeSH$$aExtracellular Matrix: metabolism
000283184 650_2 $$2MeSH$$aRats
000283184 650_2 $$2MeSH$$aNeuronal Plasticity
000283184 650_2 $$2MeSH$$aLong-Term Potentiation
000283184 650_2 $$2MeSH$$aProteolysis
000283184 650_2 $$2MeSH$$aAstrocytes: metabolism
000283184 650_2 $$2MeSH$$aHippocampus: metabolism
000283184 650_2 $$2MeSH$$aHippocampus: physiology
000283184 650_2 $$2MeSH$$aMale
000283184 650_2 $$2MeSH$$aSynapses: metabolism
000283184 650_2 $$2MeSH$$aReceptors, N-Methyl-D-Aspartate: metabolism
000283184 650_2 $$2MeSH$$aNeurons: metabolism
000283184 7001_ $$00009-0006-7399-2145$$aPerelló-Amorós, Bartomeu$$b1
000283184 7001_ $$0P:(DE-2719)2810528$$aSchneeberg, Jenny$$b2$$udzne
000283184 7001_ $$0P:(DE-2719)2814120$$aMirzapourdelavar, Hadi$$b3$$udzne
000283184 7001_ $$00000-0002-7433-2716$$aSeidenbecher, Constanze I$$b4
000283184 7001_ $$00000-0002-1815-4409$$aFejtová, Anna$$b5
000283184 7001_ $$0P:(DE-2719)2810577$$aDityatev, Alexander$$b6
000283184 7001_ $$00000-0002-1268-7511$$aFrischknecht, Renato$$b7
000283184 773__ $$0PERI:(DE-600)2025376-X$$a10.1038/s44319-025-00644-w$$gVol. 27, no. 1, p. 163 - 185$$n1$$p163 - 185$$tEMBO reports$$v27$$x1469-221X$$y2026
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