Lab of Neuronal Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.
Department of Neurochemistry and Molecular Cell Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.
Sci Rep. 2017 Oct 3;7(1):12646. doi: 10.1038/s41598-017-04007-x.
Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.
眼优势可塑性在出生后早期的关键期很容易观察到。软骨素硫酸盐（CS）是细胞外结构中最丰富的成分，称为周围神经网（PNNs），它包围表达钙结合蛋白的中间神经元（PV 细胞）。CS 在关键期在 PNNs 中积累，但在早期生命中的作用尚不清楚。在这里，我们使用缺乏关键 CS 合成酶 CSGalNAcT1 的小鼠表明，CS 的减少会损害眼优势可塑性的启动。双光子在体成像显示，与野生型小鼠相比，CS 减少的 PV 细胞的视觉反应较弱。用同源盒蛋白 Otx2 恢复了可塑性的起始，Otx2 结合主要的 CS 蛋白聚糖聚集蛋白聚糖并促进其进一步表达。CS 的持续积累与 Otx2 共同双向促进可塑性的起始和消退，并被增强 GABA 功能的地西泮取代。因此，CS 和 Otx2 可能通过促进整个生命周期中 PV 细胞的功能，作为关键期起始和消退的共同诱导物。
