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）对个人和社会都具有毁灭性的影响。因为病理学和 相对于可检测到的症状，神经损伤发生得如此之早，因此尽早研究很重要 疾病进展，重点是检测和治疗。最早的症状之一 这种疾病出现的是空间导航障碍，这可能是由于 导航计算、记忆编码或检索或某些组合的障碍 导航和记忆障碍。皮质和海马体对于记忆都很重要 编码和导航计算，这两个区域之间的相互作用支持 这些过程。在导航中，海马体参与创建认知表征 环境。顶叶皮层参与这种认知表征的翻译 根据以身体为中心的位置做出适当的导航决策。此外， 研究表明，啮齿动物睡眠期间这些区域之间的相互作用受到损害 对 AD 的 Tau 和淀粉样蛋白 (Aβ) 聚集方面进行建模。因此，我们将检验假设 导航过程中海马-皮质相互作用受损是空间缺陷的基础 Tau 和 Aβ 聚集模型小鼠中的导航（TAβA；AIM 1）。此外，我们将测试 假设这些相互作用可以通过 40Hz 刺激任一顶叶皮层来挽救 或海马体 (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，以及它如何影响认知症状。此外，该项目将 深入了解 AD 的新初步治疗方法如何改善 TAβA 效应 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.