记忆的形成是一个相当奇妙又神秘的过程。一直以来，有很多的研究人员致力于破解这个过程中的一个又一个谜团。现在，蒙特利尔的一个研究组发现一种能够抑制新的信息转化成长期记忆的蛋白质——GCN2可能是将短期记忆变成长期记忆的一个主控调节因子。他们的研究结果公布在8月25日的Nature杂志上。研究首次证明这种蛋白质合成对记忆形成的调节至关重要。这一新发现依赖于多个国家研究人员的通力合作。
Costa-Mattioli说，不是所有人们获得的新信息都以长期记忆的形式被储存起来。例如，当让一些人记下书上的一段文字后，在最初的一段时间内人们能够背诵出这个段落，但是这种记忆并没有完全储存在大脑中，因此还需要花费更多的时间记忆。
在一系列实验中，研究人员证明没有GCN2蛋白的转基因小鼠获得的新信息没有像正常小鼠那样容易“退色”，即这种新信息更频繁地被转化成了长期记忆。因此，研究人员推测GCN2可能阻止新信息被储存成长期记忆。
大脑中长期记忆的形成需要同时活化便利记忆储存的分子和沉默像GCN2这样抑制记忆储存的蛋白质。尽管目前离进行人类试验还相当遥远，但是研究人员相信他们的发现将可能为各种与记忆有关的疾病提供一种治疗方法。GCN2蛋白在长期记忆形成中功能的发现将可能帮助研究人员开发出提高记忆力丧失的病人提高记忆力。
Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins1, 2. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2-/- mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2-/- slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2-/- mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2-/- mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway
原文：
Translational control of hippocampal synaptic plasticity and memory by the eIF2 kinase GCN2, Nature 436, 1166-1173 (25 August 2005)
原文下载
GCN2基本信息
有关这个基因的全部信息：http://db.yeastgenome.org/cgi-bin/singlepageformat?sgdid=S000002691
或：http://www.pdg.cnb.uam.es/UniPub/iHOP/gs/32291.html
GCN2 GO evidence and references
phenotype/phenotype.pl?dbid=S000002691">GCN2 Phenotype details and references
GCN2 All Interactions details and references
有关作者单位的简介：
Studies on various forms of synaptic plasticity have shown a link between messenger RNA translation, learning and memory. Like memory, synaptic plasticity includes an early phase that depends on modification of pre-existing proteins, and a late phase that requires transcription and synthesis of new proteins1, 2. Activation of postsynaptic targets seems to trigger the transcription of plasticity-related genes. The new mRNAs are either translated in the soma or transported to synapses before translation. GCN2, a key protein kinase, regulates the initiation of translation. Here we report a unique feature of hippocampal slices from GCN2-/- mice: in CA1, a single 100-Hz train induces a strong and sustained long-term potentiation (late LTP or L-LTP), which is dependent on transcription and translation. In contrast, stimulation that elicits L-LTP in wild-type slices, such as four 100-Hz trains or forskolin, fails to evoke L-LTP in GCN2-/- slices. This aberrant synaptic plasticity is mirrored in the behaviour of GCN2-/- mice in the Morris water maze: after weak training, their spatial memory is enhanced, but it is impaired after more intense training. Activated GCN2 stimulates mRNA translation of ATF4, an antagonist of cyclic-AMP-response-element-binding protein (CREB). Thus, in the hippocampus of GCN2-/- mice, the expression of ATF4 is reduced and CREB activity is increased. Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway
