PDF(Pubmed)
Abstract：
Fast-spiking parvalbumin interneurons are critical for the function of mature cortical inhibitory circuits. Most of these neurons are enwrapped by a specialized extracellular matrix (ECM) structure called perineuronal net (PNN), which can regulate their synaptic input. In this study, we investigated the relationship between PNNs, parvalbumin interneurons, and synaptic distribution on these cells in the adult primary visual cortex (V1) of quadruple knockout mice deficient for the ECM molecules brevican, neurocan, tenascin-C, and tenascin-R. We used super-resolution structured illumination microscopy (SIM) to analyze PNN structure and associated synapses. In addition, we examined parvalbumin and calretinin interneuron populations. We observed a reduction in the number of PNN-enwrapped cells and clear disorganization of the PNN structure in the quadruple knockout V1. This was accompanied by an imbalance of inhibitory and excitatory synapses with a reduction of inhibitory and an increase of excitatory synaptic elements along the PNNs. Furthermore, the number of parvalbumin interneurons was reduced in the quadruple knockout, while calretinin interneurons, which do not wear PNNs, did not display differences in number. Interestingly, we found the transcription factor Otx2 homeoprotein positive cell population also reduced. Otx2 is crucial for parvalbumin interneuron and PNN maturation, and a positive feedback loop between these parameters has been described. Collectively, these data indicate an important role of brevican, neurocan, tenascin-C, and tenascin-R in regulating the interplay between PNNs, inhibitory interneurons, synaptic distribution, and Otx2 in the V1.
摘要：
快速尖峰小清蛋白中间神经元对于成熟的皮质抑制回路的功能至关重要。这些神经元中的大多数被称为神经周网（PNN）的专门的细胞外基质（ECM）结构包裹，可以调节它们的突触输入。在这项研究中,我们研究了PNN之间的关系，小白蛋白中间神经元，和突触分布在缺乏ECM分子brevican的四重敲除小鼠的成年初级视觉皮层（V1）中，Neurocan,生腱C,和腱蛋白-R我们使用超分辨率结构化照明显微镜（SIM）来分析PNN结构和相关的突触。此外,我们检查了小白蛋白和钙视网膜素中间神经元群体。我们观察到四重敲除V1中PNN包裹细胞数量的减少和PNN结构的明显混乱。伴随着抑制性和兴奋性突触的不平衡，抑制性突触的减少和兴奋性突触元素的增加。此外，小白蛋白中间神经元的数量在四重敲除中减少，而钙视网膜蛋白中间神经元，不磨损PNN，没有显示数量差异。有趣的是,我们发现转录因子Otx2同源异型蛋白阳性细胞群也减少。Otx2对于小白蛋白中间神经元和PNN成熟至关重要，并且已经描述了这些参数之间的正反馈回路。总的来说，这些数据表明brevican的重要作用，Neurocan,生腱C,和tenascin-R在调节PNN之间的相互作用中，抑制性中间神经元，突触分布,和Otx2在V1中。
