Consolidation of CS and US representations in associative fear conditioning
Consolidation of CS and US representations in associative fear conditioning
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DOI：
10.1002/hipo.10208
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发表时间：
2004-01-01
期刊：
影响因子：
3.5
通讯作者：
Silva, AJ
中科院分区：
文献类型：
--
作者：
Frankland, PW;Josselyn, A;Silva, AJ
人们对将情节记忆的不同组成部分的表征融合在一起所必需的联想过程给予了很大的关注。在目前的研究中，我们关注的是组成恐惧条件反射的个体成分的持久表征的形成过程。在单次情境恐惧条件反射实验中，如果电击是在动物被放置在新的条件反射设备中后立即传递的，那么对环境的弱条件反射就会发生，这种现象被称为即时休克缺陷。我们表明，小鼠的即刻休克缺陷可以通过预先暴露于上下文或休克来缓解。在使用这种方法将情境恐惧条件作用任务在时间上分解为其组成的表征和联想过程时，我们能够直接考察对形成情境条件刺激(CS)或非条件刺激(US)的持久表征至关重要的过程。我们的数据表明，上下文或休克的持久表征的形成涉及蛋白质合成依赖的过程。此外，cAMP反应元件结合蛋白(CREB)的遗传破坏，这是一种转录因子，调节长期记忆所需的新蛋白质的合成，破坏持久上下文记忆的形成。我们继续表明，应激激素肾上腺素调节上下文记忆的巩固，并逆转CREB缺陷小鼠的巩固缺陷。最后，我们发现，干扰NMDA或钙/钙调蛋白依赖的激酶11(CaMKII)功能都会损害上下文记忆的巩固。综上所述，这些数据表明，这种方法特别适合于表征刺激表征形成的分子和细胞过程。(C)2004年Wiley-Liss公司
Much attention has been paid to the associative processes that are necessary to fuse together representations of the various components of an episodic memory. In the present study, we focus on the processes involved in the formation of lasting representations of the individual components that make up a fear-conditioning episode. In one-trial contextual fear conditioning experiments, weak conditioning to context occurs if the shock is delivered immediately following placement of the animal in a novel conditioning apparatus, a phenomenon known as the immediate shock deficit. We show that the immediate shock deficit in mice may be alleviated by pre-exposure to either the context or shock. In using this approach to temporally dissect a contextual fear-conditioning task into its constituent representational and associative processes, we are able to examine directly the processes that are important for formation of lasting representations of the context conditioned stimulus (CS) or unconditioned stimulus (US). Our data indicate that the formation of a lasting representation of the context or shock engages protein synthesis-dependent processes. Furthermore, genetic disruption of cAMP-responsive element binding protein (CREB), a transcription factor that regulates the synthesis of new proteins required for long-term memory, disrupts the formation of lasting context memories. We go on to show that the stress hormone epinephrine modulates the consolidation of a context memory, and reverses consolidation deficits in the CREB-deficient mice. Finally we show that disrupting either NMDA or calcium/calmodulin-dependent kinase 11 (CaMKII) function impairs consolidation of context memories. Together, these data suggest that this approach is particularly suited for the characterization of molecular and cellular processes underlying the formation of stimulus representations. (C) 2004 Wiley-Liss, Inc.