Tracking the onset of spatial memory deficits in aging and Alzheimers disease models with single neuron resolution electrophysiology

利用单神经元分辨率电生理学追踪衰老和阿尔茨海默病模型中空间记忆缺陷的发生

• 批准号: 10887869
• 负责人: Theodore Joseph Zwang
• 金额: $ 24.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10887869
• 关键词: Adult; Affect; Age; Age of Onset; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease risk; American; Animal Model; Behavioral; Biological Models; Biotechnology; Brain; Brain region; Cells; Characteristics; Chronic; Clinical; Clinical Trials; Cognition; Communication; Communities; Data; Dementia; Disease Progression; Electronics; Electrophysiology (science); Foreign Bodies; Foundations; Functional disorder; Goals; Heterogeneity; Hippocampus; Histology; Human; Immune; Impaired cognition; Impairment; Individual; Injectable; Lead; Learning; Longitudinal Studies; Medial; Medical; Memory; Memory impairment; Modeling; Monitor; Mus; Neurodegenerative Disorders; Neurofibrillary Tangles; Neuronal Dysfunction; Neurons; Pathologic; Pathology; Population; Process; Research; Research Personnel; Resistance; Resolution; Syringes; Techniques; Technology; Testing; Time; Training; Work; age related; aged; aging and technology; aging brain; aging hippocampus; aging population; behavioral study; career; entorhinal cortex; excitatory neuron; experience; experimental study; innovation; insight; middle age; mouse model; neural circuit; neuron loss; neuronal circuitry; normal aging; novel; pathological aging; physical science; prevent; response; skills; spatial memory; spatiotemporal; tau Proteins; tau aggregation; tau mutation; tool; virtual reality

Project Summary/Abstract Aging changes the adult brain both structurally and functionally. Something about these changes promotes cognitive decline and increases the risk of Alzheimer’s disease, a neurodegenerative disease that affects millions of Americans and is the leading cause of dementia among adults. I propose to carry out longitudinal electrophysiology and behavioral studies to understand how age-related changes in individual neurons and their circuits contribute to cognitive impairments in mouse models of aging and Alzheimer’s disease. I plan to take advantage of a novel biotechnology, mesh electronics, that will overcome many previous challenges preventing the study of aging processes of single neurons and their circuits. I will use this technology combined with behavioral tasks in virtual reality to understand how neurons and their circuits within the hippocampus and entorhinal cortex change with normal aging and lead to cognitive decline. Then I will perform similar studies to understand how spatial memory and learning deficits arise in a model of early aging in Alzheimer’s disease that expresses pathological tau, with the goal of determining if either soluble or aggregated tau leads to neuronal dysfunction and spatial memory impairment or if they arise coincidentally. These data will be extremely valuable for the medical community as aggregated tau is currently the target of several ongoing clinical trials. These experiments will also establish mesh electronics as a useful tool for the study of normal and pathological aging that could be extended to understand the onset of cognitive decline in many other model systems.

项目总结/文摘