Decoding Hippocampal-Parietal contributions to spatial navigation in a mouse modeling Tau and AB aggregation features of Alzheimer's Disease

项目概要/摘要 阿尔茨海默病（AD）对个人和社会都是毁灭性的。因为病理学和 神经损伤相对于可检测到的症状发生得如此之早，因此早期研究非常重要。 疾病进展，重点是检测和治疗。最早的症状之一， 出现在这种疾病是空间导航的障碍，这可能是由于 导航计算、记忆编码或检索的损伤，或 导航和记忆障碍大脑皮层和海马体对记忆都很重要 编码和导航计算，这两个区域之间的交互支持 这些过程。在导航中，海马体参与创造一种认知表征， 环境保护顶叶皮层参与了这种认知表征的翻译 基于以身体为中心的位置进入适当的导航决策。此外，委员会认为， 这些区域之间的相互作用在啮齿类动物的睡眠中被削弱 对AD的Tau和淀粉样蛋白β（Aβ）聚集方面进行建模。因此，我们将测试假设 在导航过程中受损的大脑皮层-皮层相互作用是空间认知缺陷的基础， 小鼠模型Tau和Aβ聚集（TAβA; AIM 1）中的导航。此外，我们将测试 假设这些相互作用可以通过40 Hz刺激顶叶皮层来挽救， 或海马（AIM 2）。这个项目将扩大我们对系统水平功能障碍的了解， TAβA的后果，以及它如何影响认知症状。此外，该项目将 深入了解旨在改善TAβA效应的AD新的初步治疗方法 空间导航和神经功能。

Project Summary/Abstract Alzheimer’s disease (AD) is devastating for both individuals and society. Because pathology and neural damage occur so early relative to detectable symptoms, it is important to study early disease progression, with a focus on detection and treatment. One of the earliest symptoms to appear in this disease is impairments in spatial navigation, which could be the result of impairments in navigational computations, memory encoding or retrieval, or some combination of navigational and memory impairments. Both cortex and hippocampus are important for memory encoding and navigational computations, with interactions between these two regions supporting these processes. In navigation, hippocampus is involved in creating a cognitive representation of the environment. Parietal cortex is involved in the translation of this cognitive representation based on body-centered location into the appropriate navigation decision. Furthermore, interactions between these regions have been shown to be impaired during sleep in rodents modeling Tau and amyloid beta (Aβ) aggregation aspects of AD. Thus, we will test the hypothesis that impaired hippocampal-cortical interactions during navigation underlie deficits in spatial navigation in a mouse modeling Tau and Aβ aggregation (TAβA; AIM 1). Additionally, we will test the hypothesis that these interactions can be rescued via 40Hz stimulation of either parietal cortex or hippocampus (AIM 2). This project will expand our knowledge of systems level dysfunction as a consequence of TAβA, and how this impacts cognitive symptoms. Furthermore, this project will provide insight into how new, preliminary treatments for AD designed to ameliorate TAβA effects systems, spatial navigation, and neural function.