Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal nets
Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal nets
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DOI：
10.1002/dneu.20361
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发表时间：
2007-04-01
影响因子：
3
通讯作者：
Schachner, Melitta
中科院分区：
文献类型：
--
作者：
Dityatev, Alexander;Brueckner, Gert;Schachner, Melitta
细胞外基质分子-包括硫酸软骨素蛋白聚糖、透明质酸和腱生蛋白-R-在与脑和脊髓中的神经元亚群相关的神经元周网（PN）中富集。在本研究中，我们发现，类似的细胞类型依赖性细胞外基质聚集体形成在分离的细胞培养物制备从出生后早期小鼠海马。从培养的第5天开始，在表达小白蛋白的中间神经元的细胞表面检测到用花紫藤凝集素标记的网格状细胞外结构的积累，2-3周后，其发展成位于胞体和近端树突的突触接触周围以及轴突起始段周围的明显的PN。生理记录和细胞内标记的PN表达神经元显示，这些是大的快速尖峰的篮状细胞的形态特征的中间神经元。为了研究活动依赖性PN形成的机制，我们进行了药理学分析，发现阻断动作电位、递质释放、Ca 2+、谷氨酸受体的可渗透AMPA亚型或L型Ca 2+、电压门控通道强烈降低了培养神经元中PN组分的细胞外积累。因此，我们认为，通过AMPA受体和L-型通道的Ca ~（2+）内流是必要的活动依赖性的PN的形成。为了研究富含硫酸软骨素的PN的功能，我们用软骨素酶ABC处理培养物，导致几种主要PN组分显著减少。去除PNs不影响体周GABA能接触的数量和分布，但增加了培养物中中间神经元的兴奋性，暗示PNs的细胞外基质参与了中间神经元活性的调节。(c)2007 Wiley Periodicals，Inc.
Extracellular matrix molecules-including chondroitin sulfate proteoglycans, hyaluronan, and tenascin-R-are enriched in perineuronal nets (PNs) associated with subsets of neurons in the brain and spinal cord. In the present study, we show that similar cell type-dependent extracellular matrix aggregates are formed in dissociated cell cultures prepared from early postnatal mouse hippocampus. Starting from the 5th day in culture, accumulations of lattice-like extracellular structures labeled with Wisteria floribunda agglutinin were detected at the cell surface of parvalbumin expressing interneurons, which developed after 2-3 weeks into conspicuous PNs localized around synaptic contacts at somata and proximal dendrites, as well as around axon initial segments. Physiological recording and intracellular labeling of PN-expressing neurons revealed that these are large fast-spiking interneurons with morphological characteristics of basket cells. To study mechanisms of activity-dependent formation of PNs, we performed pharmacological analysis and found that blockade of action potentials, transmitter release, Ca2+, permeable AMPA subtype of glutamate receptors or L-type Ca2+, voltage gated channels strongly decreased the extracellular accumulation of PN components in cultured neurons. Thus, we suggest that Ca2+, influx via AMPA receptors and L-type channels is necessary for activity-dependent formation of PNs. To study functions of chondroitin sulfate-rich PNs, we treated cultures with chondroitinase ABC that resulted in a prominent reduction of several major PN components. Removal of PNs did not affect the number and distribution of perisomatic GABAergic contacts but increased the excitability of interneurons in cultures, implicating the extracellular matrix of PNs in regulation of interneuronal activity. (c) 2007 Wiley Periodicals, Inc.