未成熟大腦具有熟練架構(gòu)自身（神經(jīng)系統(tǒng)）以適應(yīng)生活環(huán)境改變的特性,，這是神經(jīng)生物學(xué)中最令人匪夷所思的一點(diǎn),。這種特性就是所謂的可塑性。然而,，未成熟大腦的這一奇特可塑性僅見于被稱為臨界期的一段短暫時(shí)間內(nèi),。例如，兒童在屬于早期臨界期的嬰幼兒階段被剝奪正常視覺刺激,，就會(huì)患上弱視,，導(dǎo)致永久性的視力缺損。目前,，研究人員通過比較經(jīng)歷視覺體驗(yàn)的幼鼠和成年鼠大腦的遺傳區(qū)域,，已經(jīng)發(fā)現(xiàn)對(duì)大腦可塑性可能起關(guān)鍵作用的遺傳活動(dòng)的差異。托馬索·彼左魯索和同事在2007年3月1日出版的《神經(jīng)元》（Neuron）雜志上發(fā)表了該研究成果,。
在試驗(yàn)過程中,，研究人員讓幼鼠和成年鼠在黑暗中生活了3天，之后每隔一段時(shí)間讓其適應(yīng)正常光線,，并對(duì)每只鼠的大腦視覺皮質(zhì)的遺傳區(qū)域反應(yīng)進(jìn)行分析,。研究人員發(fā)現(xiàn)幼鼠大腦有特異性遺傳活動(dòng)，而成年鼠大腦則沒有。此外,，研究人員還意外發(fā)現(xiàn)這一視覺體驗(yàn)?zāi)軌虼碳び资蟠竽X里的組蛋白發(fā)生化學(xué)修飾,，而成年鼠則無此發(fā)現(xiàn)。
組蛋白經(jīng)由DNA纏繞,，從而形成串珠樣結(jié)構(gòu)的核小體,。組蛋白的化學(xué)修飾使DNA能夠接觸激活基因的區(qū)域。研究人員同時(shí)發(fā)現(xiàn),，受視覺刺激激活的基因能夠調(diào)控其他基因的轉(zhuǎn)錄,。轉(zhuǎn)錄是將DNA基因復(fù)制成RNA的過程，是制造蛋白的一張藍(lán)圖,。為了確定組蛋白的化學(xué)修飾是否對(duì)大腦可塑性產(chǎn)生功能上的影響,，研究人員做了一個(gè)試驗(yàn)，即讓成年鼠服用一種能夠增加組蛋白化學(xué)修飾的藥物,。結(jié)果顯示,，成年鼠的視覺可塑性確實(shí)有所增加。
彼左魯索和同事下結(jié)論道：視覺體驗(yàn)可在不同程度上激活幼鼠和成年鼠大腦視皮質(zhì)中調(diào)控基因表達(dá)的胞內(nèi)信號(hào)傳導(dǎo)通路,，并且這種發(fā)育調(diào)節(jié)可以調(diào)節(jié)成年鼠大腦視皮質(zhì)的可塑性發(fā)育,。神經(jīng)系統(tǒng)的重新架構(gòu)有賴于組蛋白的化學(xué)修飾，而視覺體驗(yàn)刺激導(dǎo)致化學(xué)修飾的能力下降與臨界期的終止具有相關(guān)性,。同時(shí),，他們還表示，我們所發(fā)現(xiàn)的這一機(jī)制可能對(duì)臨界期的視皮質(zhì)可塑性具有重要意義,，產(chǎn)生于臨界期終止階段的可塑性發(fā)育調(diào)節(jié)可能是由作用于細(xì)胞膜內(nèi),、外的不同水平的多分子機(jī)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
