Activity‐dependent formation and functions of chondroitin sulfate‐rich extracellular matrix of perineuronal nets

Abstract

Extracellular matrix molecules--including chondroitin sulfate proteoglycans, hyaluronan, and tenascin-R--are enriched in perineuronal nets (PNs) associated with subsets of neurons in the brain and spinal cord. In the present study, we show that similar cell type-dependent extracellular matrix aggregates are formed in dissociated cell cultures prepared from early postnatal mouse hippocampus. Starting from the 5th day in culture, accumulations of lattice-like extracellular structures labeled with Wisteria floribunda agglutinin were detected at the cell surface of parvalbumin-expressing interneurons, which developed after 2-3 weeks into conspicuous PNs localized around synaptic contacts at somata and proximal dendrites, as well as around axon initial segments. Physiological recording and intracellular labeling of PN-expressing neurons revealed that these are large fast-spiking interneurons with morphological characteristics of basket cells. To study mechanisms of activity-dependent formation of PNs, we performed pharmacological analysis and found that blockade of action potentials, transmitter release, Ca2+ permeable AMPA subtype of glutamate receptors or L-type Ca2+ voltage-gated channels strongly decreased the extracellular accumulation of PN components in cultured neurons. Thus, we suggest that Ca2+ influx via AMPA receptors and L-type channels is necessary for activity-dependent formation of PNs. To study functions of chondroitin sulfate-rich PNs, we treated cultures with chondroitinase ABC that resulted in a prominent reduction of several major PN components. Removal of PNs did not affect the number and distribution of perisomatic GABAergic contacts but increased the excitability of interneurons in cultures, implicating the extracellular matrix of PNs in regulation of interneuronal activity.

Total number, distribution, and phenotype of cells expressing chondroitin sulfate proteoglycans in the normal human amygdala

“…Finally, in the present study, the specificity of WFA lectin histochemistry for CSPGs is demonstrated by control experiments with chondroitinase ABC, an enzyme that degrades chondroitin sulfate glycosaminoglycan chains and is routinely used to investigate the effects of elimination of CSPGs (e.g. Crespo, et al, 2007, Dityatev, et al, 2007, Hamai, et al, 1997, Pizzorusso, et al, 2002, Sugahara, et al, 1994. In our chondroitinase ABC-treated tissue, we could detect no intracellularly-labeled glia, and only rare, faintly labeled perineuronal nets.…”

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference

“…In line with our finding is the well-established observation that PNNs predominantly enwrap PV neurons in the cortex and hippocampus (Bruckner et al, 1996;Van den Oever et al, 2010), suggesting a shared molecular process that regulates condensation of structural ECM proteins at PV neurons in the cortex. Changes in PNNs have been shown to affect the firing properties of PV cells, thereby influencing GABAergic control over pyramidal cell activity (Dityatev et al, 2007). Indeed, in the mPFC, degradation of PNNs results in reduced inhibitory input onto pyramidal cells and this impairs acquisition of cocaine CPP memory (Slaker et al, 2015).…”

Lewisxand α2,3-Sialyl Glycans and Their Receptors TAG-1, Contactin, and L1 Mediate CD24-Dependent Neurite Outgrowth

“…Cerebellar and DRG neurons were prepared from 5-to 7-d-old wild-type, TAG-1-, Contactin-, or Caspr-deficient mice as described previously (Chen et al, 1999;Kleene et al, 2001). Hippocampal neurons were prepared from 1-to 2-d-old wild-type mice (Dityatev et al, 2007) and neurons from spinal cord were prepared from 14-d-old wild-type embryos (Simova et al, 2006). Cortical neurons were prepared from 17-d-old wild-type embryos.…”