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

解码海马顶叶对阿尔茨海默病 Tau 和 AB 聚集特征建模小鼠空间导航的贡献

• 批准号: 10707032
• 负责人: Sarah Danielle Cushing
• 金额: $ 3.95万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-19 至 2025-08-18
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707032
• 关键词: 3xTg-AD mouse; Abeta clearance; Affect; Age; Algorithms; Alzheimer' s Disease; Amyloid beta-Protein; Animal Model; Auditory; Behavior; Brain; Brain region; Cells; Cognitive; Communication; Complex; Data; Detection; Disease; Disease Progression; Early identification; Early treatment; Environment; Exposure to; Functional disorder; Goals; Head; Hippocampus; Human; Impaired cognition; Impairment; Individual; Knowledge; Learning; Light; Location; Memory; Memory impairment; Mus; Neurobehavioral Manifestations; Neurobiology; Neurofibrillary Tangles; Neurons; Neurophysiology - biologic function; Parietal; Parietal Lobe; Pathology; Pattern; Photic Stimulation; Physiologic pulse; Poisson Distribution; Process; Research; Research Project Grants; Rodent; Rodent Diseases; Rodent Model; Sleep; Societies; Symptoms; System; Testing; Transgenic Mice; Translations; Visual; Wakefulness; Work; abeta accumulation; cognitive function; density; design; functional disability; human model; improved; information processing; insight; member; memory encoding; memory retrieval; mouse model; multisensory; neural; prevent; tau Proteins; tau aggregation; treatment strategy; way finding

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.

项目摘要/摘要 阿尔茨海默氏病（AD）对个人和社会都是毁灭性的。因为病理和 相对于可检测的症状，神经损害发生得如此早。 疾病进展，重点是检测和治疗。最早的症状之一 出现在这种疾病中的是空间导航的损害，这可能是 导航计算，记忆编码或检索的损害，或某种组合 导航和记忆力障碍。皮质和海马都对记忆很重要 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，海马参与了创建的认知表示 环境。顶叶皮质参与了这种认知表达的翻译 基于以身体为中心的位置到适当的导航决定。此外， 这些区域之间的相互作用已显示在啮齿动物的睡眠期间受到损害 建模AD的TAU和淀粉样β（Aβ）聚集方面。那就是我们将检验假设 导航期间的海马皮层相互作用损害了空间上的定义 在小鼠建模tau和Aβ聚集的小鼠中导航（TAβA； AIM 1）。此外，我们将测试 可以通过40Hz刺激任何两层皮质来挽救这些相互作用的假设 或海马（AIM 2）。该项目将扩大我们对系统级功能障碍的了解 TAβA的结果，以及这如何影响认知症状。此外，这个项目将 提供有关如何改善TAβA效应的AD的新的初步治疗 系统，空间导航和神经功能。