Conjunctive Representations in Cortex and Hippocampus

皮层和海马体的联合表征

• 批准号: 6892122
• 负责人: JERRY Weeks RUDY
• 金额: $ 30.62万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-10 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892122
• 关键词: amygdala; behavioral /social science research tag; conditioning; discrimination learning; excitatory aminoacid; experience; fluorescent in situ hybridization; genetic regulation; glutamate receptor; hippocampus; histology; laboratory rat; learning; memory; microinjections; neocortex; neural information processing; neural plasticity; protein structure function; regulatory gene; western blottings

DESCRIPTION (provided by applicant): The hippocampus is critical to what is termed declarative memory, our ability to consciously recall the events of our lives and to connect us with our past. It is also vulnerable to the deleterious effects of Alzheimer's dementia, stress, alcohol, stroke and other brain insults. Thus, this region of the brain continues to be a major target for gaining insights into the biological basis of memory that could lead to treatments, which could benefit people with memory disorders. The proposed research focuses on the hippocampus and to a lesser extend its interactions with the amygdala, with the goal of advancing our basic understanding of memory processes. Our specific aims are directed at three issues. In Aim 1 we will determine the contributions gluatamate receptors (NMDA and AMPA) in the hippocampus and amygdala make to the mnemonic and non-mnemonic functions of these regions by studying their roles in contextual fear conditioning and memory for context. In Aim 2 we will study memory maintenance processes that may be important for stabilizing hippocampal-dependent memories. This work is based on recent findings that for several days following a learning experience the resulting memory are vulnerable to disruption. These studies will investigate the hypothesis that glutamate receptor activation is critical to memory maintenance. In Aim 3 we focus on hippocampal dependent memories to investigate a novel hypothesis about the function of certain immediate early genes (lEGs), specifically, that one function of lEGs is to prime the memory system to facilitate the storage of subsequent events. It has two components: (a) experience at time 1 can influence the storage of a subsequent event experienced at time 2 and (b) this effect is mediated by lEGs. We propose experiments to test the implications of both components. This work will contribute to a more complete understanding of the basic mechanisms that support declarative memory and indirectly to the development of treatments to ameliorate memory disorders.

描述(申请人提供)：海马体对所谓的陈述性记忆至关重要，我们有意识地回忆生活中的事件并将我们与过去联系起来的能力。它还容易受到阿尔茨海默氏症、压力、酒精、中风和其他大脑侮辱的有害影响。因此，大脑的这一区域仍然是深入了解记忆的生物学基础的主要目标，这可能会导致治疗，从而使记忆障碍患者受益。这项拟议的研究侧重于海马体，并较少扩展其与杏仁核的相互作用，目的是促进我们对记忆过程的基本理解。我们的具体目标是针对三个问题。在目标1中，我们将通过研究谷氨酸受体(NMDA和AMPA)在情境恐惧条件反射和情境记忆中的作用，来确定海马体和杏仁体中的谷氨酸受体对这些区域的助记和非助记功能的贡献。在目标2中，我们将研究记忆维持过程，这可能是稳定海马体依赖记忆的重要过程。这项工作是基于最近的发现，即在学习经历后的几天里，由此产生的记忆很容易受到干扰。这些研究将调查谷氨酸受体激活对记忆维持至关重要的假设。在目标3中，我们专注于海马依赖记忆，以探索关于某些即刻早期基因(腿)功能的新假说，具体地说，腿的功能之一是启动记忆系统，以促进后续事件的存储。它有两个组成部分：(A)时间1的经验可以影响在时间2经历的后续事件的储存；(B)这种影响是通过腿来调节的。我们建议进行实验来测试这两个组件的含义。这项工作将有助于更全面地了解支持陈述性记忆的基本机制，并间接有助于开发改善记忆障碍的治疗方法。