Single-cell and target-specific resolution of multiple memories across the brain

大脑中多个记忆的单细胞和目标特异性分辨率

• 批准号: 10689742
• 负责人: Christine Ann Denny
• 金额: $ 75.82万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10689742
• 关键词: Address; Age-associated memory impairment; Alzheimer' s Disease; Area; Atlases; Behavior; Behavioral; Behavioral Assay; Biological; Brain; Brain Mapping; Brain imaging; Brain region; Catalogs; Cells; Cognition; Cognition Disorders; Development; Disease; Documentation; FOS gene; Fluorescence-Activated Cell Sorting; Funding; Genetic; Genetically Engineered Mouse; Goals; Histologic; Image; Immediate-Early Genes; Immunohistochemistry; Individual; Label; Laboratories; Lead; Learning; Maps; Mediating; Memory; Mental Depression; Mental disorders; Microscopic; Modeling; Molecular; Molecular Biology; Mus; National Institute of Mental Health; Neurons; Neurosciences; Optics; Organism; Performance; Physiological; Play; Population; Positive Lymph Node; Post-Traumatic Stress Disorders; Research; Research Personnel; Resolution; Retrieval; Role; Structure; System; Techniques; Technology; Time; Transgenic Organisms; United States National Institutes of Health; Viral; Virus; Visualization; Work; biological systems; combinatorial; experience; experimental study; genetic approach; in vivo; innovation; insight; memory encoding; memory retrieval; network models; neural; neural network; neuromechanism; novel; optogenetics; programs; tool

PROJECT SUMMARY / ABSTRACT A tremendous amount of research has provided us with an understanding of how neurons work in concert during the formation and retrieval of individual memories. While we understand how memories are stored in a limited number of brain regions, we do not yet understand how multiple memory traces are stored across whole-brain neural networks, as well as their real-time physiological dynamics, genetic landscape, and preferential wiring. What is needed now is technology to bridge the gap in our understanding between microscopic interactions at the neuronal level and macroscopic structures that perform computations across networks involved in learning and memory. Using a combination of two activity-dependent tagging systems that utilize the immediate early genes (IEG) Arc and c-fos, the aim of this proposal is to address the critical need for obtaining a map of multiple memories and provide the dynamic states of the brain in the context of behavioral performance and memory expression. We will first utilize behavioral assays and whole-brain imaging to provide unprecedented insight on how multiple memories (e.g., positive and negative memories) are stored with single-cell resolution in a brain-wide manner. Identification of similarities and differences between populations and projections of positive and negative memory ensembles will be quantified and correlated with behavioral performance by using neuronal modeling developed in the Denny laboratory. Tagged cells will also be pulled down and sequenced to delineate the genetic landscape differentiating positive and negative memories. We will then use in vivo Ca2+ imaging to resolve the real-time dynamics (e.g., Ca2+ activity) of neural ensembles as they participate in positive and negative memory encoding and retrieval. Moreover, we will use optogenetic modulation to manipulate the positive or negative ensembles in a within-subject manner during behavioral performance to identify key nodes involved in memory expression. Finally, we will use viral tracing strategies to determine how these ensembles are structurally wired across brain, thereby providing a wiring diagram for multiple experiences in the brain. In summary, comprehensive molecular biology, immunohistochemistry, network modeling, Ca2+ imaging, and optogenetic techniques will be utilized. As most studies have narrowed their analyses to a single brain structure, these studies will expand this scope exponentially by analyzing whole-brain memory traces mediating multiple memories. This combinatory system will result in a whole-brain atlas for individual memories, including positive and negative memories, with single- cell resolution.

项目摘要/摘要

项目成果

Social reactivation of fear engrams enhances memory recall.

• DOI: 10.1073/pnas.2114230119
• 发表时间: 2022-03-22
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1
• 作者: Finkelstein AB;Leblanc H;Cole RH;Gallerani T;Vieira A;Zaki Y;Ramirez S
• 通讯作者: Ramirez S

Chronic activation of fear engrams induces extinction-like behavior in ethanol-exposed mice.

• DOI: 10.1002/hipo.23263
• 发表时间: 2021-01
• 期刊: Hippocampus
• 影响因子: 3.5
• 作者: Cincotta C;Murawski NJ;Grella SL;McKissick O;Doucette E;Ramirez S
• 通讯作者: Ramirez S

Hippocampal fear engrams modulate ethanol-induced maladaptive contextual generalization in mice.

海马恐惧印迹调节小鼠乙醇诱导的适应不良情境泛化。

• DOI: 10.1002/hipo.23463
• 发表时间: 2022
• 期刊: Hippocampus
• 影响因子: 3.5
• 作者: Cincotta,Christine;Ruesch,Evan;Senne,Ryan;Ramirez,Steve
• 通讯作者: Ramirez,Steve