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.

对于负责长期存储信息的机制鲜为人知 新皮层。我们实验室的最新研究表明，除了其在海马中的作用外， α钙钙调蛋白激酶II（ACAMKII）对于皮质可塑性至关重要 新皮质网络中的合并。在这里，我们建议将行为神经科学的组合结合在一起 工具，体内延时2光子激光扫描显微镜（2p LSM），可诱导和特定区域 分子方法可以揭示Acamkii在皮质记忆存储中的作用。这个特定的目的 提案是： 特定的目标＃1-确定远程恢复前扣带回和腹膜后皮质的功能 老鼠的记忆。我们的初步结果表明，这两个结构是远程内存所需的。 现在，我们想定义他们在这个知之甚少的记忆阶段中的角色。 具体目的＃2-确定Acamkii在遥控中的前扣带回和骨后皮质中的作用 记忆。我们的良好结果证明了该激酶在远程内存中的作用。这些研究将是 至关重要的是确定需要该激酶的位置以及如何调节远程内存。 特定的目标＃3-在体内2p LSM中使用延时，以发现Acamkii在突触重组中的作用 在前扣带和腹膜后皮质中（与Joshua Trachtenberg博士密切合作， 该提议和开拓2P LSM的先驱。有广泛的证据表明camkii 调节SynaAptic Retructuros。现在，我们将在体内表征这些事件并测试其影响 在远程内存上。 这里提出的实验代表了分子和细胞研究的第一步 记忆在皮质网络中存储的机制。除了对 了解遥不可及的记忆，这些研究的结果对于了解认知很重要 与年龄相关的认知下降和进行性神经退行性疾病有关的疾病 作为阿尔茨海默氏病，由于这些疾病会影响我们的区域和记忆过程 建议学习。