Modification of extracellular matrix by enzymatic removal of chondroitin sulfate and by lack of Tenascin-R differentially affects several forms of synaptic plasticity in the hippocampus
Modification of extracellular matrix by enzymatic removal of chondroitin sulfate and by lack of Tenascin-R differentially affects several forms of synaptic plasticity in the hippocampus
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DOI：
10.1016/s0306-4522(01)00082-3
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Dityatev, A
中科院分区：
文献类型：
--
作者：
Bukalo, O;Schachner, M;Dityatev, A
细胞外基质是一个复杂的大分子网络，包括糖蛋白、多糖和蛋白聚糖。 Tenascin-R 和硫酸软骨素蛋白多糖是海马细胞外基质的重要组成部分，共定位于中间神经元的神经周网络中。与野生型小鼠相比，腱蛋白-R 表达缺陷的突变小鼠表现出由海马 CA1 区辐射层中的 Schaffer 络脉的 theta 爆发刺激引起的长时程增强减少两倍。在用软骨素酶 ABC 预处理 2 小时的野生型小鼠切片中观察到同样的增强作用降低，该酶完全去除了细胞外基质中的硫酸软骨素。与来自这些小鼠的未经处理的切片相比，用该酶处理来自生腱蛋白-a缺陷的动物的切片并没有进一步降低增强作用，这表明去除生腱蛋白-R和硫酸软骨素所产生的效果被阻断。然而，在野生型中，在θ爆发刺激后立即记录的增强水平显着高于生腱蛋白-R缺陷小鼠，而碳化酶ABC对这种短期形式的可塑性没有显着影响。酶治疗也不会影响低频刺激引起的短期抑郁，而腱蛋白-R 缺陷小鼠的突触可塑性却降低了。相比之下，CA1 的长期抑制因硫酸软骨素的消化而受损，但在生腱蛋白-R 突变体中表现正常。我们的数据表明，生腱蛋白-R 和硫酸软骨素蛋白聚糖差异调节多种形式的突触可塑性，表明涉及不同的机制。 (C) 2001 国际广播组织。由爱思唯尔科学有限公司出版。保留所有权利。
The extracellular matrix is a complex network of macromolecules including glycoproteins, polysaccharides and proteoglycans. Tenascin-R and chondroitin sulfate proteoglycans are essential components of hippocampal extracellular matrix co-localised in perineuronal nets on interneurons. Mutant mice deficient in expression of tenascin-R showed a two-fold reduction of long-term potentiation induced by theta-burst stimulation of Schaffer collaterals in the stratum radiatum of the CA1 region of the hippocampus, as compared to wild-type mice. The same reduction in potentiation was observed in slices from wild-type mice pretreated for 2 h with chondroitinase ABC that completely removed chondroitin sulfates from the extracellular matrix. Treatment of slices from tenascin-a deficient animals with the enzyme did not further reduce potentiation in comparison with untreated slices from these mice, showing an occlusion of effects produced by removal of tenascin-R and chondroitin sulfates. However, the level of potentiation recorded immediately after theta-burst stimulation was significantly higher in wild-type than in tenascin-R deficient mice, whereas cbondroitinase ABC had no significant effect on this short-term form of plasticity. Enzymatic treatment also did not affect short-term depression evoked by low-frequency stimulation, whereas this farm of synaptic plasticity was reduced in tenascin-R deficient mice. In contrast, long-term depression in CA1 was impaired by digestion of chondroitin sulfates but appeared normal in tenascin-R mutants.Our data demonstrate that tenascin-R and chondroitin sulfate proteoglycans differentially modulate several forms of synaptic plasticity, suggesting that different mechanisms are involved. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.