Pittenger C, Kandel E
Howard Hughes Medical Institute, Center for Neurobiology and Behavior, Columbia University College, New York, NY 10032, USA.
C R Acad Sci III. 1998 Feb-Mar;321(2-3):91-6. doi: 10.1016/s0764-4469(97)89807-1.
Current models of brain function hold that learning corresponds to changes in the efficacy of single synapses. The study of learning and of a variety of forms of synaptic plasticity has revealed that both have at least two phases: an early phase that is not dependent on protein synthesis and a late phase that depends on new transcription and translation. Our laboratory has examined synaptic plasticity in Aplysia and in mice to better understand the regulatory events that lead to the induction of the late, protein synthesis-dependent phase of synaptic plasticity. Our recent studies of Aplysia have revealed that the genes that control the late phase of synaptic facilitation are controlled by both an activator, ApCREB1, and a repressor, ApCREB2. This leads to a model in which the late phase of synaptic facilitation is initiated by a perturbation of the balance between activators and repressors of transcription; this perturbation can be accomplished by regulating the activator, the repressor, or both. We, and others, have shown that this transcriptional switch is conserved, at least in part, in the regulation of synaptic plasticity in mice: CREB is implicated in activation of genes required for LTP, a model for synaptic plasticity in the mammalian hippocampus. We speculate that a similar balance between activators and repressors may regulate the genes required for long-term memory in mammals.
当前的脑功能模型认为，学习与单个突触效能的变化相对应。对学习和各种形式的突触可塑性的研究表明，两者至少都有两个阶段：一个不依赖蛋白质合成的早期阶段和一个依赖新转录和翻译的晚期阶段。我们实验室研究了海兔和小鼠的突触可塑性，以更好地理解导致突触可塑性晚期、蛋白质合成依赖性阶段诱导的调控事件。我们最近对海兔的研究表明，控制突触易化晚期的基因受一种激活因子ApCREB1和一种抑制因子ApCREB2共同控制。这就产生了一个模型，其中突触易化的晚期是由转录激活因子和抑制因子之间平衡的扰动引发的；这种扰动可以通过调节激活因子、抑制因子或两者来实现。我们以及其他人已经表明，这种转录开关在小鼠突触可塑性的调控中至少部分是保守的：CREB与长时程增强（LTP）所需基因的激活有关，LTP是哺乳动物海马体中突触可塑性的一个模型。我们推测，激活因子和抑制因子之间类似的平衡可能调节哺乳动物长期记忆所需的基因。
