Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice

• Published in: Cell reports (Cambridge) 2024-05, Vol.43 (5), p.114112-114112, Article 114112
• Main Authors: Chelini, Gabriele, Mirzapourdelavar, Hadi, Durning, Peter, Baidoe-Ansah, David, Sethi, Manveen K., O’Donovan, Sinead M., Klengel, Torsten, Balasco, Luigi, Berciu, Cristina, Boyer-Boiteau, Anne, McCullumsmith, Robert, Ressler, Kerry J., Zaia, Joseph, Bozzi, Yuri, Dityatev, Alexander, Berretta, Sabina
• Format: Article
• Language: English
• Subjects: Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - physiology; chondrotin sulfate proteoglycans; CP: Cell biology; CP: Neuroscience; CS clusters; extracellular matrix; Extracellular Matrix - metabolism; hippocampus; Hippocampus - metabolism; Hippocampus - physiology; immunoprecipitation; learning and memory; Long-Term Potentiation - physiology; Male; Memory - physiology; Mice; Mice, Inbred C57BL; Neuronal Plasticity - physiology; sensory manipulation; Synapses - metabolism; Synapses - physiology; synaptic plasticity; versican
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114112

Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca2+ signaling, vesicle cycling, and AMPA-receptor exocytosis, thus suggesting a role in long-term potentiation (LTP). Finally, we show that, in the CA1 hippocampal region, the attenuation of CS56 glycoepitopes, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in mice. These findings show that activity-dependent remodeling of the peri-synaptic ECM regulates the induction and consolidation of LTP, contributing to hippocampal-dependent memory. [Display omitted] •Glia-derived chondroitin sulfate (CS) proteoglycans form aggregates of peri-synaptic matrix•Clusters of peri-synaptic matrix arise in an experience-dependent fashion•Versican core protein regulates the expression of a specific 6-sulfated CS glycoform•6-sulfated CS contributes to spatially organized synaptic refinement Chelini et al. demonstrate that versican regulates the expression of a specific proteoglycan glycoform, contributing to long-term potentiation and hippocampal-dependent memory in mice. These findings bring attention to a potential mechanism contributing to the spatial arrangement of synaptic ensembles during the active phase of experience-dependent plasticity.