Proteoglycan Clusters as a Site of Coordinated, Multi-Dendritic Plasticity

Abstract

Experience-dependent learning depends on synaptic plasticity. While plasticity in individual synapses has been extensively investigated, the mechanisms underlying coordinated changes across sets of synapses on multiple dendrites, likely needed to encode effective adaptations to a salient stimulus, are not well understood. The extracellular matrix is uniquely well suited to fulfill this function, as rapid glia-driven remodeling of its local composition powerfully impact synaptic plasticity. We show that extracellular matrix microenvironments, named CS6 clusters, dynamically form around several dendrites in response to sensory stimuli in coincidence to stimulus-driven synaptic plasticity. CS6 clusters, formed by glia-dependent secretion of extracellular matrix components surrounding sets of adjacent dendrites, may represent a novel structure supporting coordinated synaptic plasticity.

Aging-Associated Changes in Cognition, Expression and Epigenetic Regulation of Chondroitin 6-Sulfotransferase Chst3

“…Since CHST3 levels are elevated in the aged hippocampus, it raises questions about its functional outcome, as previous studies have shown that there is an age-dependent reduction in 6-sulfated GAGs as well as increased PNN content [7,14]. As a recent study indicates VCAN as the major carrier of 6-sulfated GAGs [59], in addition to the consistent correlation between Chst3 and Vcan expression levels observed in this study, we used VCAN as the CHST3 substrate to estimate the functionality of CHST3. By staining hippocampal slices for VCAN and C6S, we discovered a high amount of VCAN core proteins in aged mice and a lower ratio of 6-sulfated GAGs relative to Vcan expression levels.…”

“…From perineuronal measurements, we observed a significant increase in VCAN core proteins levels in 22-24 M-old We then studied the CHST3 functionality in aged animals by immunolabeling of its chondroitin-6 sulfates and one of its substrates, the lectican VCAN. VCAN appeared as the best choice as a recent study indicates VCAN is the major carrier of 6-O-sulfates [59]. We measured the perineuronal, periaxonal, and perisynaptic VCAN and C6S content in a 0.6 µm proximity around PV+ interneurons (Figure 7A,C,E).…”