Gene Targeting Approaches to Learning and Memory Studies

学习和记忆研究的基因靶向方法

• 批准号: 8658342
• 负责人: ALCINO J. SILVA
• 金额: $ 54.17万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-25 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658342
• 关键词: Affect; Age-associated memory impairment; Alzheimer' s Disease; Anterior; Area; Behavioral; Binding; Ca(2+)-Calmodulin Dependent Protein Kinase; Calcium; Cognition Disorders; Collaborations; Complement; Data; Event; Gene Targeting; Growth; Hippocampus (Brain); Image; Immediate-Early Genes; Information Storage; Laboratories; Laser Scanning Microscopy; Learning; Lesion; Lidocaine; Medial; Memory; Methods; Molecular; Mus; Muscimol; Mutation; N-Methylaspartate; Neocortex; Neurodegenerative Disorders; Neurosciences; Pharmacogenetics; Phase; Phosphotransferases; Photons; Physiology; Play; Prefrontal Cortex; Process; Retrieval; Role; Somatosensory Cortex; Staging; Structure; Synapses; Synaptic plasticity; System; Testing; Time; Training; Vertebral column; Visual; Xenopus; calmodulin-dependent protein kinase II; cingulate cortex; conditioning; design; experience; in vivo; inhibitor/antagonist; memory process; mutant; neocortical; new technology; null mutation; research study; retinotectal; somatosensory; time use; tool; two-photon

There is very little known about the mechanisms responsible for the very long-term storage of information in the neocortex. Recent studies from our laboratory suggest that besides its role in the hippocampus, the alpha calcium calmodulin kinase II (aCaMKII) is critical for cortical plasticity and for remote memory consolidation in neocortical networks. Here, we propose to use a combination of behavioral neuroscience tools, in vivo time-lapse 2 photon laser scanning microscopy (2P LSM), inducible and region-specific molecular approaches to unravel the role of aCaMKII in cortical memory storage. The specific aims of this proposal are: Specific Aim #1- To determine the function of the anterior cingulate and retrosplinial cortex in remote memory in mice. Our preliminary results indicate that these two structures are required for remote memory. Now we would like to define their roles in this poorly understood memory phase. Specific Aim #2- To determine the role of aCaMKII in anterior cingulate and retrosplinial cortex in remote memory. Our previoous results demonstrated a role for this kinase in remote memory. These studies will be critical to determine where this kinase is needed and how it modulates remote memory. Specific Aim #3- To use time lapse in vivo 2P LSM to uncover the role of aCaMKII in synaptic restructuring in anterior cingulate and retrosplinial cortex, (close collaboration with Dr. Joshua Trachtenberg, a co-Pi in this proposal and a pioneer in the ground breaking 2P LSM). There is extensive evidence that CAMKII modulates synaaptic retructuring. Now, we would to characterize these events in vivo and test their impact on remote memory. The experiments proposed here represent some of the first steps in the study of the molecular and cellular mechanisms underlying the storage of memories in cortical networks. Besides their impact on the understanding of remote memory, the results from these studies will be important to understand cognitive disorders associated with age-related cognitive decline and progressive neurodegenerative disorders such as Alzheimer's disease, since these conditions affect the regions and the memory processes that we propose to study.

人们对于长期存储信息的机制知之甚少。 新皮质。我们实验室最近的研究表明，除了在海马体中的作用外， α 钙调蛋白激酶 II (aCaMKII) 对于皮质可塑性和远程记忆至关重要 新皮质网络的巩固。在这里，我们建议结合行为神经科学 工具，体内延时 2 光子激光扫描显微镜 (2P LSM)、诱导型和区域特异性 分子方法揭示 aCaMKII 在皮质记忆存储中的作用。本次活动的具体目标 提案是： 具体目标#1 - 确定远端前扣带回和夹层后皮层的功能 老鼠的记忆。我们的初步结果表明，这两种结构是远程存储器所必需的。 现在我们想定义它们在这个人们知之甚少的记忆阶段中的角色。 具体目标 #2 - 确定 aCaMKII 在远程前扣带回和夹层后皮质中的作用 记忆。我们之前的结果证明了这种激酶在远程记忆中的作用。这些研究将 对于确定哪里需要这种激酶以及它如何调节远程记忆至关重要。 具体目标 #3 - 使用体内延时 2P LSM 揭示 aCaMKII 在突触重组中的作用 在前扣带皮层和后夹层皮质中，（与 Joshua Trachtenberg 博士密切合作，他是 这项提案也是突破性 2P LSM 的先驱）。有大量证据表明 CAMKII 调节突触重构。现在，我们将在体内描述这些事件并测试它们的影响 在远程存储器上。 这里提出的实验代表了分子和细胞研究的一些第一步。 皮层网络中记忆存储的机制。除了它们对 理解远程记忆，这些研究的结果对于理解认知能力非常重要 与年龄相关的认知能力下降和进行性神经退行性疾病相关的疾病，例如 例如阿尔茨海默氏病，因为这些疾病会影响我们的区域和记忆过程 建议去学习。