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

项目摘要/摘要 衰老在结构和功能上都改变了成年人的大脑。关于这些变化的一些东西 促进认知衰退并增加阿尔茨海默病的风险，阿尔茨海默病是一种神经退行性疾病， 影响数以百万计的美国人，是成年人痴呆症的主要原因。我建议进行 纵向电生理学和行为研究以了解个体年龄相关的变化 在衰老和阿尔茨海默病小鼠模型中，神经元及其电路导致认知障碍。 我计划利用一种新的生物技术，网状电子学，它将克服以前的许多挑战 阻止对单个神经元及其电路衰老过程的研究。我将结合使用这项技术 通过虚拟现实中的行为任务来了解海马体内的神经元及其电路 内嗅皮层随正常衰老而改变，并导致认知功能下降。然后我会进行类似的研究 了解阿尔茨海默病早期衰老模型中空间记忆和学习障碍是如何产生的 表达病理性tau，目的是确定是可溶的tau还是聚集的tau导致神经元 功能障碍和空间记忆障碍，或者如果它们巧合出现的话。这些数据将非常有价值 对于医学界来说，聚集的tau目前是几个正在进行的临床试验的目标。这些 实验还将建立网状电子学作为研究正常和病理性衰老的有用工具。 这可以扩展到理解许多其他模型系统中认知衰退的开始。

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.