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

项目摘要/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 神经损伤发生得如此之早，相对于可检测到的症状，及早研究是很重要的。 疾病进展，重点是检测和治疗。最早的症状之一是 在这种疾病中出现的是空间导航的损害，这可能是 导航计算、记忆编码或检索方面的障碍，或以下几种情况的组合 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，海马体参与创建一种认知表征 环境。顶叶皮质参与了这种认知表征的翻译 根据车身中心位置进行适当的导航决策。此外， 这些区域之间的相互作用已被证明在啮齿类动物的睡眠中受到损害 模拟AD的Tau和淀粉样β蛋白(Aβ)聚集方面。因此，我们将检验这一假设 在导航过程中损害了海马区-大脑皮层的相互作用是空间缺陷的基础 在模拟Tau和Aβ聚合的鼠标中导航(TAβA；目标1)。此外，我们还将测试 这种相互作用可以通过40赫兹刺激顶叶皮质来挽救的假说 或海马区(AIM 2)。该项目将扩展我们对系统级功能障碍的了解 TAβA的后果，以及这如何影响认知症状。此外，该项目将 深入了解AD的新的初步治疗方法是如何改善TAβA效应的 系统、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.