Molecular heterogeneity of aggrecan‐based perineuronal nets around five subclasses of parvalbumin‐expressing neurons in the mouse hippocampus
Chondroitin sulfate (CS) is a linear polysaccharide containing repeating disaccharide units of N‐acetyl‐D‐galactosamine (GalNAc) and D‐glucuronic acid (GlcA) residues (Ogawa et al., 2010). The perineuronal net (PNN) is a specialized structure of the extracellular matrix that is enriched with CS‐bearing proteoglycans (CSPG) that consist of core proteins, glycoforms, and hyaluronan (Giamanco and Matthews, 2012). It has been repeatedly shown that PNNs play a critical role in regulation of neural plasticity (Bandtlow and Zimmermann, 2000; Wang and Fawcett, 2012) and neuroprotection (Morawski et al., 2004; Cabungcal et al., 2013). Over 20 years ago, PNNs that were labeled by the plant lectin Wisteria floribunda agglutinin (WFA) were reported to be closely associated with PV+ GABAergic neurons (Hartig et al., 1992). However, despite the growing interest in the functional significance of WFA+ PNNs, few studies on WFA+ PNNs have taken into account of the diversity of PV+ GABAergic neurons. We thus recently addressed this issue in the hippocampus, and found that the vast majority of PV+ basket cells were surrounded by WFA+ PNNs, while PV+ axo‐axonic cells, oriens‐lacunosum‐moleculare (O‐LM) cells, and hippocampo‐septal projection (H‐S) cells often lacked WFA+ PNNs (Yamada and Jinno, 2015).
In the central nervous system, the main CSPGs are the lectican family, which includes aggrecan, versican, neurocan, and brevican (Ruoslahti, 1996; Nakamura et al., 2000; Yamaguchi, 2000). Unlike other lecticans, aggrecan is found almost exclusively in PNNs, and it is therefore thought to play a unique role in the formation and function of this structure (Bruckner et al., 1993; Morawski et al., 2012a). To date, several studies have reported the molecular heterogeneity of PNNs (Bruckner et al., 2000). For instance, the monoclonal antibody Cat‐315 recognizes oligosaccharide epitopes on aggrecan and a glycoform of receptor protein tyrosine phosphatase β/phosphacan, while Cat‐301 recognizes the core protein of aggrecan (ACAN) (Matthews et al., 2002; Yin et al., 2006; Saitoh et al., 2008). WFA recognizes GalNAc comprising CS chains on aggrecan, because neurons from aggrecan‐deficient mice lack WFA labeling (Young and Williams, 1985; Giamanco et al., 2010). Despite these studies, the molecular heterogeneity of PNNs around PV+ GABAergic neurons has not yet been fully understood.
In this study, we compared the formation of WFA+ PNNs and ACAN+ PNNs around five subclasses of PV+ GABAergic neurons in the hippocampus. We also examined the relative densities of GABAergic synapses covering PV+ neurons in combination with the experimental digestion of WFA+ PNNs. The molecular heterogeneity of aggrecan‐based PNNs surrounding PV+ GABAergic neurons may provide information essential for our understanding of the functional significance of PNNs in the hippocampus.