Gene Expression in Long-term Memory

长期记忆中的基因表达

• 批准号: 6468294
• 负责人: CRISTINA M ALBERINI
• 金额: $ 33.69万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6468294
• 关键词: amygdala; antisense nucleic acid; behavior test; behavioral /social science research tag; behavioral genetics; biological signal transduction; cAMP response element binding protein; cyclin dependent kinase; enhancer binding protein; fear; gene expression; hippocampus; immunocytochemistry; insulinlike growth factor; intermolecular interaction; laboratory rat; long term memory; memory; oligonucleotides; phosphorylation; protein binding; protein biosynthesis; protein protein interaction; protein structure function; temporal lobe /cortex; transcription factor; western blottings

DESCRIPTION (provided by applicant): Long-term memory formation consists of multiple phases. A new memory is initially labile. To become stable this new memory undergoes a process known as consolidation that, in the case of declarative memories, occurs within the medial temporal lobes and requires gene expression. When recalled, memories reenter a new phase of vulnerability and seem to require a "reconsolidation" process in order to be maintained. The goal of this project is to characterize, particularly in the temporal lobe regions hippocampus and amygdala, the gene expression regulation underlying different phases of long-term memory formation. It has been shown that members of the transcription factor family cAMP response element binding protein (CREB) play an essential role in the consolidation of long-term memory. However, the cascade of events activated downstream of CREB is still poorly understood. In Inhibitory Avoidance (IA) learning, a significant and persistent activation (phosphorylation) of CREB and CREB-dependent gene expression occur in the hippocampus. We have recently found that a CREB-downstream evolutionarily conserved molecular event essential for IA long-term memory consolidation is the induction of another transcription factor, a member of the CCAAT enhancer binding protein (C/EBPBeta). Preliminary data suggest that, together with C/EBPBeta, another member of the C/EBP family C/EBPdelta, may play a role in memory consolidation. We have also identified a number of putative CREB-C/EBPdownstream genes. Two of these, Insulin-like growth factor-Il (IGF-II) and cyclin-dependent kinase 5 (CDK5), may have a critical role as modulators of the synaptic morphological changes that underlie memory storage. In contrast, the molecular mechanisms of "reconsolidation" are not yet known. In this project we propose to continue our characterization of the gene cascade underlying memory formation, and specifically to: 1- Characterize the anatomical and temporal profiles of CREB-C/EBPBeta activation and asses the contribution of this molecular pathway to the storage of medial temporal lobe-dependent memories; 2- Determine whether C/EBPdelta plays an essential role as a memory activator or repressor. 3- Determine the role of the target genes CDK5 and IGF-II. 4. Characterize the molecular basis of the memory "reconsolidation" process. The proposed experiments will provide significant insight into the molecular mechanisms of memory consolidation. An understanding of the molecular changes underlying memory formation may indicate new strategies for the treatment of memory disorders.

描述（由申请人提供）：长期记忆形成包括 多个阶段。最初是一个新的内存。要变得稳定这个新的 内存经历一个称为合并的过程 声明的记忆发生，发生在内侧颞叶内，需要基因 表达。召回时，记忆重新进入了一个新的脆弱性阶段和 似乎需要“重新溶解”过程才能维护。目标 这个项目的特征是，尤其是在颞叶区域 海马和杏仁核，基因表达调节的基因表达不同 长期记忆形成的阶段。已经表明 转录因子家庭cAMP响应元件结合蛋白（CREB）播放 在巩固长期记忆中的重要作用。但是， CREB下游激活的一系列事件仍然很了解。在 抑制性避免（IA）学习，一种重大而持续的激活 CREB和CREB依赖性基因表达的（磷酸化）发生在 海马。我们最近发现，一个creb downstream从进化上 IA长期记忆巩固必不可少的保守分子事件是 诱导另一个转录因子，CCAAT增强子的成员 结合蛋白（C/EBPBETA）。初步数据表明， C/EBPBETA是C/EBP家族C/EBPDELTA的另一个成员，可能在 内存合并。我们还确定了许多推定的 CREB-C/EBPDownstream基因。其中两个，胰岛素样生长因子-IL （IGF-II）和细胞周期蛋白依赖性激酶5（CDK5）可能具有关键作用 基于内存存储的突触形态变化的调节器。 相反，“重新溶解”的分子机制尚不清楚。 在这个项目中，我们建议继续我们对基因级联的表征 基础记忆形成，特别是：1-表征 CREB-C/EBPBETA激活的解剖学和时间概况，并评估 该分子途径对内侧时间储存的贡献 叶依赖的记忆； 2-确定c/ebpdelta是否扮演必不可少的 作为内存激活器或阻遏物的角色。 3-确定目标的作用 基因CDK5和IGF-II。 4。表征记忆的分子基础 “重新合并”过程。提出的实验将提供重要的 深入了解记忆巩固的分子机制。一种理解 分子变化的基础记忆形成可能表明新的 治疗记忆障碍的策略。