未成熟大脑具有熟练架构自身（神经系统）以适应生活环境改变的特性，这是神经生物学中最令人匪夷所思的一点。这种特性就是所谓的可塑性。然而，未成熟大脑的这一奇特可塑性仅见于被称为临界期的一段短暂时间内。例如，儿童在属于早期临界期的婴幼儿阶段被剥夺正常视觉刺激，就会患上弱视，导致永久性的视力缺损。目前，研究人员通过比较经历视觉体验的幼鼠和成年鼠大脑的遗传区域，已经发现对大脑可塑性可能起关键作用的遗传活动的差异。托马索·彼左鲁索和同事在2007年3月1日出版的《神经元》（Neuron）杂志上发表了该研究成果。
在试验过程中，研究人员让幼鼠和成年鼠在黑暗中生活了3天，之后每隔一段时间让其适应正常光线，并对每只鼠的大脑视觉皮质的遗传区域反应进行分析。研究人员发现幼鼠大脑有特异性遗传活动，而成年鼠大脑则没有。此外，研究人员还意外发现这一视觉体验能够刺激幼鼠大脑里的组蛋白发生化学修饰，而成年鼠则无此发现。
组蛋白经由DNA缠绕，从而形成串珠样结构的核小体。组蛋白的化学修饰使DNA能够接触激活基因的区域。研究人员同时发现，受视觉刺激激活的基因能够调控其他基因的转录。转录是将DNA基因复制成RNA的过程，是制造蛋白的一张蓝图。为了确定组蛋白的化学修饰是否对大脑可塑性产生功能上的影响，研究人员做了一个试验，即让成年鼠服用一种能够增加组蛋白化学修饰的药物。结果显示，成年鼠的视觉可塑性确实有所增加。
彼左鲁索和同事下结论道：视觉体验可在不同程度上激活幼鼠和成年鼠大脑视皮质中调控基因表达的胞内信号传导通路，并且这种发育调节可以调节成年鼠大脑视皮质的可塑性发育。神经系统的重新架构有赖于组蛋白的化学修饰，而视觉体验刺激导致化学修饰的能力下降与临界期的终止具有相关性。同时，他们还表示，我们所发现的这一机制可能对临界期的视皮质可塑性具有重要意义，产生于临界期终止阶段的可塑性发育调节可能是由作用于细胞膜内、外的不同水平的多分子机制所引起的。
部分英文原文：
Developmental Downregulation of Histone Posttranslational Modifications Regulates Visual Cortical Plasticity
Elena Putignano1, Giuseppina Lonetti2, Laura Cancedda1, Gianmichele Ratto2, Mario Costa2, Lamberto Maffei1, 2 and Tommaso Pizzorusso2, 3,
1Scuola Normale Superiore, Neurobiology Laboratory, Area Ricerca CNR, via Moruzzi, 1 Pisa 56125, Italy
2Istituto Neuroscienze CNR, Area Ricerca CNR, via Moruzzi, 1 Pisa 56125, Italy
3University of Florence, Department of Psychology, via S. Niccolò, 93 50125 Florence, Italy
Received 7 August 2006; revised 22 December 2006; accepted 8 February 2007. Published: February 28, 2007. Available online 28 February 2007.
Summary
The action of visual experience on visual cortical circuits is maximal during a critical period of postnatal development. The long-term effects of this experience are likely mediated by signaling cascades regulating experience-dependent gene transcription. Developmental modifications of these pathways could explain the difference in plasticity between the young and adult cortex. We studied the pathways linking experience-dependent activation of ERK to CREB-mediated gene expression in vivo. In juvenile mice, visual stimulation that activates CREB-mediated gene transcription also induced ERK-dependent MSK and histone H3 phosphorylation and H3-H4 acetylation, an epigenetic mechanism of gene transcription activation. In adult animals, ERK and MSK were still inducible; however, visual stimulation induced weak CREB-mediated gene expression and H3-H4 posttranslational modifications. Stimulation of histone acetylation in adult animals by means of trichostatin promoted ocular dominance plasticity. Thus, differing, experience-dependent activations of signaling molecules might be at the basis of the differences in experience-dependent plasticity between juvenile and adult cortex.
Author Keywords: MOLNEURO; SIGNALING; DEVBIO
