Role of the Perisynaptic Extracellular Matrix in Synaptic Plasticity

神经周围网络（PNN）是成人脑细胞外基质的特化。它们富含分泌糖蛋白，如Tenascin-R，和蛋白聚糖，如brevican或neurocan。尽管PNN是在大的神经元体和神经突周围形成的，但其成分的主要部分来自神经胶质细胞。这些网状结构在功能上是在屏障形成的背景下讨论的，但最近的数据指出PNN成分在突触可塑性中的积极作用。因此，我们建议(1)研究与分离原代培养中兴奋性和抑制性突触形成相关的PNN出现的条件，作为模型系统。此外，(2)我们希望寻找brevican的（周围）突触结合伙伴，它们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brevican对突触可塑性的作用。此外(4)，我们提出了一项详细的表型研究小鼠品系缺乏布雷维蛋白聚糖，神经蛋白聚糖或两种蛋白聚糖有关受影响的大脑可塑性特性的变化。我们的小鼠实验将包括海马结构的解剖研究、突触蛋白组分组成的生化分析、体外LTP测量、脑电图记录和详细的行为测试，以阐明含蛋白聚糖的PNN对成年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.