Role of the Perisynaptic Extracellular Matrix in Synaptic Plasticity

神经元周网（Perineuronalnets，PNN）是成人脑细胞外基质的特化。它们富含分泌的糖蛋白，如腱生蛋白-R，和蛋白聚糖，如短蛋白聚糖或神经聚糖。虽然PNN形成于大的神经元胞体和神经突周围，但其主要成分来自神经胶质细胞。在功能上，这些网状结构的背景下，障碍的形成进行了讨论，但最近的数据点PNN组件在突触可塑性的积极作用。因此，我们建议（1）研究PNN出现的条件与兴奋性和抑制性突触的形成在分离的原代培养作为一个模型系统。此外，（2）我们希望寻找短蛋白聚糖的（β-）突触结合伴侣，其可能作为突触接触周围的PNN锚定点;（3）研究基质金属蛋白酶切割短蛋白聚糖对突触可塑性的作用。此外（4），我们提出了一个详细的表型研究小鼠品系缺乏短蛋白聚糖，神经聚糖或两种蛋白聚糖的影响大脑的可塑性的变化。我们的小鼠实验将包括海马结构的解剖学研究，突触蛋白组分的组成的生化分析，体外LTP测量，EEG记录和详细的行为测试，以阐明含蛋白多糖的PNN对成人神经元可塑性的贡献。

Perineuronal nets (PNN) are specializations of the adult brain extracellular matrix. They are rich in secreted glycoproteins, like Tenascin-R, and proteoglycans, like brevican or neurocan. Although PNN are formed around large neuronal somata and neurites, a major fraction of their constituents derive from glial cells. Functionally these net-like structures are discussed in the context of barrier-formation, but recent data point to an active role of PNN components in synaptic plasticity. We therefore propose (1) to investigate the conditions for PNN emergence in relation to the formation of excitatory and inhibitory synapses in dissociated primary cultures as a model system. Furthermore, (2) we want to search for (peri-) synaptic binding partners for brevican, which might act as PNN-anchoring points around synaptic contacts and (3) investigate the role of brevican cleavage by matrix metalloproteases for synaptic plasticity. Moreover (4), we propose a detailed phenotypical investigation of mouse lines deficient for brevican, neurocan or both proteoglycans with respect to changes in the plastic properties of the affected brains. Our mouse experiments will include anatomical studies of the hippocampus architecture, biochemical analysis of the composition of synaptic protein fractions, in vitro LTP measurements, EEG recordings and a detailed behavioral testing to elucidate the contribution of proteoglycan-containing PNN to adult neuronal plasticity.