FUNCTIONAL CODING IN HIPPOCAMPAL /CORTICAL SYSTEMS

海马/皮质系统的功能编码

• 批准号: 3726585
• 负责人: HOWARD EICHENBAUM
• 金额: --
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3726585
• 关键词: aging; animal old age; behavior test; cerebral cortex; cerebral degeneration; cognition disorders; computational neuroscience; hippocampus; laboratory rat; limbic system; memory; memory disorders; molecular psychobiology; neural information processing; neural plasticity; olfactory stimulus; single cell analysis

The general aim of this project is to characterize age-related alterations in learning and memory capacity and associated changes in neural coding by hippocampal/cortical systems presumed to underlie the cognitive decline. Previous work from this laboratory and elsewhere indicates that the hippocampal system mediates declarative memory and that hippocampal processing central declarative memory is reflected in neuronal activity dependent on conjunctions and/or relations among critical cues in different behavioral paradigms. The proposed experiments are aimed at testing the specific hypothesis that age- related cognitive decline is attributable to a disproportionate deterioration of declarative memory and corresponding loss of conjunctional-relational correlates of hippocampal unit activity, disruption of cortic-limbic coordination, and reduced induction or rapid decay of learning related plasticity in hippocampus and cortex. In a series of empirical studies we propose to test this hypothesis by assessing the behavioral performance of young adult and ages rats in four odor- and spatially-guided learning tasks that impose different kinds of demands on hippocampal processing. We will also characterize the behavioral correlates of single neurons, the relationship between sensory and hippocampal rhythms, and synaptic efficacy of hippocampal and cortical circuitry in rats performing those tasks. Our analyses will focus on comparisons of the data from behaviorally "impaired" and "unimpaired" old rats with that from young mature adults. In parallel computational modeling studies, we propose to develop multiple network models that stimulate hippocampal neural activity and examine the effects of analogues of age-related circuitry changes on processing performance. Our initial studies will compare the effects of aging-like alterations on the processing performance of several simplified models of hippocampal networks. Further studies will involve the development and assessment of the effects of these alterations in more realistic hippocampal models. Our goal is to build models of the hippocampus that stimulate, and therefore can be validated by, the data from recording studies. We will assess the effects of both individual changes that occur in aging and combinations of them to identify the critical determinants of cognitive decline.

该项目的总体目的是表征与年龄有关的 学习和记忆能力的改变以及相关的变化 海马/皮质系统的神经编码是为了 认知能力下降。 该实验室和其他地方的先前工作 表明海马系统介导声明性记忆和 海马处理中央声明性记忆反映在 神经元活动取决于连词和/或关系 不同行为范式中的关键提示。 提议 实验旨在检验年龄的特定假设 相关的认知下降归因于不成比例的 声明性记忆的恶化和相应的损失 海马单位活性的共同关系相关性， 皮质 - 夹层协调的破坏，并降低诱导或快速 在海马和皮层中学习相关可塑性的衰减。 在一系列实证研究中，我们建议通过 评估年轻成人和年龄大鼠的行为表现 施加不同的四个气味和空间引导的学习任务 海马加工的需求。 我们还将描述 单个神经元的行为相关性， 感觉和海马节奏以及海马的突触功效 和执行这些任务的大鼠的皮质电路。 我们的分析 将重点介绍来自行为“受损”和 年轻成年人的“未损坏”的老鼠。 在平行的计算建模研究中，我们建议开发 刺激海马神经活动和 检查与年龄相关电路变化对类似物的影响 处理性能。 我们的最初研究将比较 对几种处理性能的类似老化的变化 海马网络的简化模型。 进一步的研究将涉及 这些改变的影响的发展和评估 更现实的海马模型。 我们的目标是建立 刺激数据的海马，因此可以通过数据验证 来自记录研究。 我们将评估两个人的影响 衰老和组合中发生的变化以识别 认知能力下降的关键决定因素。