Abstract
The neural extracellular matrix (ECM) is enriched with hyaluronic acid, chondroitin sulfate proteoglycans (CSPGs) and the glycoprotein tenascin-R, which play important roles in synaptic plasticity, as shown by studies of the CA1 region of the hippocampus. However, ECM molecules are strongly expressed in the CA2 region, which harbors a high number of fast-spiking interneurons (FSIs) surrounded by a particularly condensed form of ECM, perineuronal nets. Despite this intriguing peculiarity, the functional role of ECM in the CA2 region is mostly unknown. Here, we investigate the acute and delayed effects of chondroitinase ABC (ChABC), an enzyme that digests chondroitin sulfate side chains of CSPGs and greatly attenuates neural ECM, on neuronal excitability and excitatory transmission in the CA2 region. Whole-cell patch clamp recordings of CA2 pyramidal cells (PCs) and FSIs in hippocampal slices revealed that 7 days after injection of ChABC into the CA2 region in vivo, there are alterations in excitability of FSIs and PCs. FSIs generated action potentials with larger amplitudes and longer durations in response to less depolarizing currents compared to controls. PCs were excited at less depolarized membrane potentials, resulted in lower latency of spike generation. The frequency of excitatory postsynaptic currents in FSIs was selectively reduced, while the frequency of inhibitory postsynaptic currents was selectively increased. Acute treatment of hippocampal slices with ChABC did not result in any of these effects. This increase in excitability and changes in synaptic inputs to FSIs after attenuation of ECM suggests a crucial role for perineuronal nets associated with FSIs in regulation of synaptic and electrical properties of these cells.
Highlights
The extracellular matrix (ECM) has a distinct role in brain development, maturation of neural circuits, and regulation of synaptic functions
Histochemical investigation of Wisteria floribunda agglutinin (WFA), brevican and aggrecan expression in rat and mouse brain reveals that chondroitin sulfate proteoglycans (CSPGs) are highly enriched in the hippocampal CA2 area compared with CA1 and CA3 (Brückner et al, 2003; Ajmo et al, 2008; Mcrae et al, 2010; Carstens et al, 2016; Noguchi et al, 2017)
WFA staining in control slices revealed the high level of perineuronal nets (PNNs) expression in the CA2 region compared to PNNs expression in CA1 and CA3 regions (Figures 1A,B)
Summary
The extracellular matrix (ECM) has a distinct role in brain development, maturation of neural circuits, and regulation of synaptic functions. The reduced firing threshold and after-hyperpolarization were reported 1–2 days after ChABC treatment (Dityatev et al, 2007), which indicated for the first time that the PNNs may control excitability of FSIs. Histochemical investigation of Wisteria floribunda agglutinin (WFA), brevican and aggrecan expression in rat and mouse brain reveals that CSPGs are highly enriched in the hippocampal CA2 area compared with CA1 and CA3 (Brückner et al, 2003; Ajmo et al, 2008; Mcrae et al, 2010; Carstens et al, 2016; Noguchi et al, 2017). Our results highlight the significant role of ECM in regulation of synaptic and electrical properties of FSIs in hippocampal CA2 area in vivo
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