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.

项目总结/文摘