Assessing the Dynamics of Hippocampal Neuronal Engrams in Memory Formation and Aging

评估海马神经元印迹在记忆形成和衰老中的动态

基本信息

批准号：
10829020
负责人：
Amy Monasterio
金额：
$ 4.87万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10829020
关键词：
Address Affect Age Age-associated memory impairment Aging Alzheimer&apos s Disease Area Behavior Brain Brain region Calcium Cells Computer Models Cues Data Disease Educational process of instructing Environment Episodic memory FOS gene Faculty Fellowship Fostering Functional disorder Future Genetic Genetic Techniques Goals Grant Health Healthcare Systems Hippocampus Image Immediate-Early Genes Impaired cognition Impairment Individual Intervention Job Application Knowledge Label Learning Life Longevity Memory Memory Loss Memory impairment Mentors Methods Modeling Mus Neurodegenerative Disorders Neurons Neurosciences Pattern Phase Physiology Population Postdoctoral Fellow Preparation Process Professional Competence Prosencephalon Research Research Personnel Research Project Grants Retrieval Rodent Role Scientist Societies Structure Synapses Techniques Technology Testing Time Training age related awake career cell type cognitive function experience experimental study genetic approach imaging approach imaging genetics in vivo insight memory recall memory retrieval mouse model negative affect novel novel strategies optical imaging recruit success treatment strategy two-photon virus genetics

项目摘要

PROJECT SUMMARY/ABSTRACT Defining how we form, store, and retrieve memories is one of neuroscience’s most researched areas. The hippocampus is a well-characterized forebrain structure with a crucial role in the formation and retrieval of episodic memory, and is known to be vulnerable to age-related memory dysfunction. Cognitive decline in age and neurodegenerative disease is an increasing burden on healthcare systems and society at large. To treat the causes of memory decline in age and age-related disease, the mechanisms by which hippocampal cell populations form and maintain individual memories over time must be characterized. Decades of research have shown that new learning results in strengthened synaptic connections between networks of hippocampal neurons. These distributed connections between cells are believed to make up the physical basis for memories, often defined as an engram. Significant progress has been made in finding the engram in the brain with the application of activity-dependent genetic strategies, which isolate populations of cells expressing immediate- early genes (IEGs), to identify the neurons activated by learning. Subpopulations of neurons expressing the IEG c-Fos are activated during learning and reactivated during memory recall, so they are often referred to as engram neurons. Previous studies demonstrated the crucial role of hippocampal engram neurons in memory recall behavior, and artificial reactivation of these cells in mouse models of aging and Alzheimer’s disease rescued memory retrieval deficits, pointing to engram cells as a promising target for future interventions to treat memory deficits. However, the in vivo mechanisms by which these cells store associations, and how their reactivation drives memory retrieval, have yet to be explored. To address this gap in knowledge, this project will utilize novel two-photon imaging to combine an inducible c-Fos tagging strategy with large-scale calcium imaging, to investigate how these cell populations contribute to memory formation. Aim 1 of this project is to characterize the dynamics of engram cell populations across learning in order to inform our understanding of circuit mechanisms underlying memory formation in healthy states. This mechanistic understanding will then be utilized in Aim 2 to define how these processes are negatively impacted by aging. Overall, the aims of this proposal will contribute to the advancement of our understanding of the circuit mechanisms of hippocampal memory formation in health and disease, with the potential to inform current treatment strategies for cognitive decline.

项目概要/摘要定义我们如何形成、存储和检索记忆是神经科学研究最多的领域之一。海马体是一种特征明确的前脑结构，在大脑信息的形成和恢复中发挥着至关重要的作用。情景记忆，并且已知容易受到与年龄相关的记忆功能障碍的影响。神经退行性疾病给医疗保健系统和整个社会带来了越来越大的负担。年龄记忆衰退的原因及与年龄相关的疾病，海马细胞的机制几十年来的研究必须对人群随着时间的推移形成和维持个体记忆进行表征。研究表明，新的学习可以增强海马网络之间的突触连接神经元之间的这些分布式连接被认为构成了记忆的物理基础，在寻找大脑印迹方面取得了重大进展应用活性依赖性遗传策略，分离表达直接表达的细胞群早期基因（IEG），以识别通过学习激活的神经元表达 IEG 的神经元亚群。 c-Fos 在学习过程中被激活，并在记忆回忆过程中重新激活，因此它们通常被称为印迹先前的研究证明了海马印迹神经元在记忆回忆中的关键作用。行为，以及在衰老和阿尔茨海默病小鼠模型中人工重新激活这些细胞记忆检索缺陷，表明印迹细胞是未来治疗记忆干预措施的一个有希望的目标然而，这些细胞储存关联的体内机制以及它们如何重新激活。驱动记忆检索，还有待探索，为了解决这一知识差距，该项目将利用新颖的方法。双光子成像将诱导型 c-Fos 标记策略与大规模钙成像相结合，研究这些细胞群如何促进记忆形成。该项目的目标 1 是表征。学习过程中印迹细胞群的动态，以帮助我们理解电路然后将利用这种机制理解健康状态下的记忆形成机制。目标 2 定义了这些过程如何受到老龄化的负面影响。总体而言，该提案的目标将是。有助于增进我们对海马记忆形成回路机制的理解在健康和疾病方面，有可能为当前认知能力下降的治疗策略提供信息。