The brain's extracellular matrix (ECM) is crucial for neural circuit functionality, synaptic plasticity, and learning. While the role of the ECM in excitatory synapses has been extensively studied, its influence on inhibitory synapses, particularly on GABAergic long-term plasticity, remains poorly understood. This study aims to elucidate the effects of ECM components on inhibitory synaptic transmission and plasticity in the hippocampal CA1 region. We focus on the roles of chondroitin sulfate proteoglycans (CSPGs) and hyaluronic acid in modulating inhibitory postsynaptic currents (IPSCs) at two distinct inhibitory synapses formed by somatostatin (SST)-positive and parvalbumin (PV)-positive interneurons onto pyramidal cells (PCs). Using optogenetic stimulation in brain slices, we observed that acute degradation of ECM constituents by hyaluronidase or chondroitinase-ABC did not affect basal inhibitory synaptic transmission. However, short-term plasticity, particularly burst-induced depression, was enhanced at PV→PC synapses following enzymatic treatments. Long-term plasticity experiments demonstrated that CSPGs are essential for NMDA-induced iLTP at SST→PC synapses, whereas the digestion of hyaluronic acid by hyaluronidase impaired iLTP at PV→PC synapses. This indicates a synapse-specific role of CSPGs and hyaluronic acid in regulating GABAergic plasticity. Additionally, we report the presence of cryptic GABAergic plasticity at PV→PC synapses induced by prolonged NMDA application, which became evident after CSPG digestion and was absent under control conditions. Our results underscore the differential impact of ECM degradation on inhibitory synaptic plasticity, highlighting the synapse-specific interplay between ECM components and specific GABAergic synapses. This offers new perspectives in studies on learning and critical period timing.

中文翻译：

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细胞外基质完整性调节海马体中的 GABA 能可塑性


大脑的细胞外基质 （ECM） 对于神经回路功能、突触可塑性和学习至关重要。虽然 ECM 在兴奋性突触中的作用已得到广泛研究，但其对抑制性突触的影响，特别是对 GABA 能长期可塑性的影响，仍然知之甚少。本研究旨在阐明 ECM 成分对海马 CA1 区抑制性突触传递和可塑性的影响。我们专注于硫酸软骨素蛋白聚糖 （CSPG） 和透明质酸在调节生长抑素 （SST） 阳性和小白蛋白 （PV） 阳性中间神经元形成的两个不同抑制性突触中的作用锥体细胞 （PC）。在脑切片中使用光遗传学刺激，我们观察到透明质酸酶或软骨素酶-ABC 对 ECM 成分的急性降解不会影响基础抑制性突触传递。然而，酶处理后 PV→PC 突触的短期可塑性，特别是爆发诱导的抑制增强。长期可塑性实验表明，CSPGs 对于 NMDA 诱导的 SST→PC 突触处的 iLTP 至关重要，而透明质酸酶对透明质酸的消化会损害 PV→PC 突触处的 iLTP。这表明 CSPG 和透明质酸在调节 GABA 能可塑性中的突触特异性作用。此外，我们报道了由长时间 NMDA 应用诱导的 PV→PC 突触存在隐蔽的 GABA 能可塑性，这在 CSPG 消化后变得明显，并且在对照条件下不存在。我们的结果强调了 ECM 降解对抑制性突触可塑性的不同影响，突出了 ECM 成分和特异性 GABA 能突触之间的突触特异性相互作用。 这为学习和关键时期时间的研究提供了新的视角。