Intrinsic cellular and molecular properties of in vivo hippocampal synaptic plasticity are altered in the absence of key synaptic matrix molecules
Intrinsic cellular and molecular properties of in vivo hippocampal synaptic plasticity are altered in the absence of key synaptic matrix molecules
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DOI：
10.1002/hipo.22742
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发表时间：
2017-08-01
期刊：
影响因子：
3.5
通讯作者：
Manahan-Vaughan, Denise
中科院分区：
文献类型：
--
作者：
Jansen, Stephan;Gottschling, Christine;Manahan-Vaughan, Denise
海马突触可塑性是信息储存的关键细胞机制。在海马体中，长时程增强（LTP）和长时程抑制（LTD）均由突触Ca 2+升高触发，而突触Ca 2+升高通常由突触后致密区的电压门控阳离子通道（如N-甲基-d-天冬氨酸受体（NMDAR））的开放介导。突触后致密物的完整性由细胞外基质（ECM）保证。在这里，我们探讨了突触可塑性是否受到成年行为小鼠缺乏ECM蛋白短蛋白，神经蛋白，腱生蛋白-C，腱生蛋白-R（KO）的影响。我们观察到，在齿状回（DG）的突触增强和抑郁症的配置文件相比，在野生型同窝仔（WT）的可塑性配置文件的深刻改变。具体地，突触抑制以频率依赖性方式放大，并且尽管在强传入强直化后表达晚期LTP（> 24小时），但由较弱强直化引起的LTP的早期组分（4小时）在WT和KO动物中是等同的。此外，后一种形式的LTP在WT而不是KO小鼠中是NMDAR依赖性的。DG受体表达的检查显示，与WT动物相比，KO中N-甲基-d-天冬氨酸受体的GluN 2A和GluN 2B亚基、代谢型谷氨酸受体mGlu 5和L型钙通道Ca（v）1.3的水平显著较低。Homer 1a和P/Q型钙通道Ca（v）1.2在KO小鼠中没有变化。总之，研究结果表明，在缺乏多种ECM蛋白的小鼠中，突触可塑性是完整的，但从根本上是不同的。
Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca2+-elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-d-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C, and tenascin-R (KO). We observed that the profiles of synaptic potentiation and depression in the dentate gyrus (DG) were profoundly altered compared to plasticity profiles in wild-type littermates (WT). Specifically, synaptic depression was amplified in a frequency-dependent manner and although late-LTP (>24hr) was expressed following strong afferent tetanization, the early component of LTP (4hr) elicited by weaker tetanization was equivalent in WT and KO animals. Furthermore, this latter form of LTP was NMDAR-dependent in WT but not KO mice. Scrutiny of DG receptor expression revealed significantly lower levels of both the GluN2A and GluN2B subunits of the N-methyl-d-aspartate receptor, of the metabotropic glutamate receptor, mGlu5 and of the L-type calcium channel, Ca(v)1.3 in KO compared to WT animals. Homer 1a and of the P/Q-type calcium channel, Ca(v)1.2 were unchanged in KO mice. Taken together, findings suggest that in mice that lack multiple ECM proteins, synaptic plasticity is intact, but is fundamentally different.