PDF(Pubmed)
Abstract：
Visual cortical plasticity is high during early life, but gradually decreases with development. This is due to the Otx2-driven maturation of intracortical inhibition that parallels the condensation of extracellular matrix components into perineuronal nets mainly around parvalbumin-positive GABAergic neurons. Repressor Element 1 Silencing Transcription (REST) epigenetically controls the expression of a plethora of neuron-specific genes. We demonstrate that the conditional knockout of REST in the primary visual cortex of adult mice induces a shift of ocular dominance after short-term monocular deprivation and promotes the recovery of vision in long-term deprived animals after reverse suture. These phenomena paralleled a reduction of perineuronal net density and increased expression of REST target genes, but not of the homeoprotein Otx2 in the visual cortex contralateral to the deprived eye. This shows that REST regulates adult visual cortical plasticity and is a potential therapeutic target to restore vision in adult amblyopia by enhancing V1 plasticity.
摘要：
在生命早期，视觉皮层可塑性很高，但随着发展逐渐减少。这是由于Otx2驱动的皮质内抑制的成熟，使细胞外基质成分凝结成神经周网，主要是在小白蛋白阳性GABA能神经元周围。抑制因子元件1沉默转录(REST)表观遗传学控制大量神经元特异性基因的表达。我们证明，成年小鼠初级视觉皮层中REST的条件性敲除会在短期单眼剥夺后引起眼优势的转移，并在反向缝合后促进长期剥夺动物的视力恢复。这些现象与神经周的净密度降低和REST靶基因表达增加平行。但不是视同型蛋白Otx2在视觉皮层对侧剥夺的眼睛。这表明REST调节成人视皮层可塑性，是通过增强V1可塑性来恢复成人弱视视力的潜在治疗靶点。
