Regulation of synapse formation, plasticity and function by astroglial-derived extracellular matrix - tenascin-C and interacting proteoglycan ligands

突触的萌发和修剪是成人神经系统中突触可塑性的重要形态相关因素。在这种情况下，电活动起着重要的调节作用。相比之下，人们对这些过程的细胞和分子基础知之甚少。干扰分析和重组技术的基因消除提供了明确的迹象，表明星形胶质细胞来源的细胞外基质成分，如ECM糖蛋白tenascin-C，参与了突触的成熟和可塑性。初步研究表明，Tenascin-C和胶质细胞来源的硫酸软骨素蛋白多糖对原代胚胎CNS神经元的轴突萌发具有调节作用。不同细胞功能的互补受体已经被鉴定。这些研究将继续下去，以确定星形胶质细胞来源的细胞外基质控制突触形成、成熟和功能的机制。将研究两种体外模型，即胚胎海马体培养和嗅球神经元培养。将使用电生理测量和先进的成像技术来评估突触发生、功能特性和突触活动的调节。将特别强调受体、突触后的生理修饰和相应的反应神经元中的下游信号通路。

The sprouting and pruning of synapses constitute important morphological correlates of synaptic plasticity in the adult nervous system. Electrical activity plays an important regulatory role in this context. By comparison, less is known about the cellular and molecular bases of these processes. Perturbation assays and gene elimination by recombinant techniques have provided clear indications that astroglialderived extracellular matrix components, e.g. the ECM glycoprotein tenascin-C, are involved in synapse maturation and plasticity. It has been shown in preliminary studies that tenascin-C and the glial-derived chondroitinsulfate proteoglycan phosphacan modulate neurite sprouting of primary embryonic CNS neurons. Complementary receptors for distinct cellular functions have been characterized. These studies shall be continued in order to characterise the mechanisms by which astrocyte-derived ECM controls synapse formation, maturation and function. Two in vitro models will be studied, namely cultures of embryonic hippocampal and of olfactory glomerular neurons. Synaptogenesis, functional properties and modulation of synaptic activity will be assessed using electrophysiological measurement and advanced imaging techniques. Particular emphasis will be given to receptors, postsynaptic physiological modifications and corresponding downstream signaling pathways in responsive neurons.