Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses
Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses
复制标题
DOI：
10.1038/s41598-019-50404-9
复制
发表时间：
2019-09-26
影响因子：
4.6
通讯作者：
Faissner, Andreas
中科院分区：
文献类型：
--
作者：
Gottschling, Christine;Wegrzyn, David;Faissner, Andreas
哺乳动物脑内的突触传递不仅限于神经元突触前和突触后的相互作用，还涉及星形胶质细胞以及细胞外基质(ECM)分子。细胞外基质中的糖蛋白、蛋白多糖和透明质酸广泛存在于细胞周围环境中，并凝聚成围绕中枢神经系统神经元亚群的特殊超结构，称为神经周围神经网(PNN)。本研究重点分析了细胞外基质分子tenascin-C(TNC)、tenascin-R(TNR)、NeuroCan和Brivican缺失的四重基因敲除小鼠的PN NS。在这里，我们分析了兴奋性突触和抑制性突触的比例，并对体外培养的海马神经元进行了自发神经元网络活动的电生理记录。虽然我们发现在四重基因敲除培养中兴奋性突触分子的数量增加，但抑制性突触分子的数量显著减少。这一观察得到了神经元网络活动水平的增强的补充。对四基因敲除小鼠海马区PNNS的体内分析表明，PNN的大小和CA2区的复杂性都有所降低。此外，对出生后第21天的海马区进行了微阵列分析，揭示了四重基因敲除的海马区基因表达的变化。
The synaptic transmission in the mammalian brain is not limited to the interplay between the pre- and the postsynapse of neurons, but involves also astrocytes as well as extracellular matrix (ECM) molecules. Glycoproteins, proteoglycans and hyaluronic acid of the ECM pervade the pericellular environment and condense to special superstructures termed perineuronal nets (PNN) that surround a subpopulation of CNS neurons. The present study focuses on the analysis of PN Ns in a quadruple knockout mouse deficient for the ECM molecules tenascin-C (TnC), tenascin-R (TnR), neurocan and brevican. Here, we analysed the proportion of excitatory and inhibitory synapses and performed electrophysiological recordings of the spontaneous neuronal network activity of hippocampal neurons in vitro. While we found an increase in the number of excitatory synaptic molecules in the quadruple knockout cultures, the number of inhibitory synaptic molecules was significantly reduced. This observation was complemented with an enhancement of the neuronal network activity level. The in vivo analysis of PNNs in the hippocampus of the quadruple knockout mouse revealed a reduction of PNN size and complexity in the CA2 region. In addition, a microarray analysis of the postnatal day (P) 21 hippocampus was performed unravelling an altered gene expression in the quadruple knockout hippocampus.