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

基本信息

项目摘要

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

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Social reactivation of fear engrams enhances memory recall.
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:
  • 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:
  • 影响因子:
    3.5
  • 作者:
    Cincotta,Christine;Ruesch,Evan;Senne,Ryan;Ramirez,Steve
  • 通讯作者:
    Ramirez,Steve
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Christine Ann Denny其他文献

(R,S)-Ketamine is Antidepressant and Prophylactic Against Stress in Adolescent but Not Aged Mice
  • DOI:
    10.1016/j.biopsych.2022.02.050
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Alessia Mastrodonato;Ina Pavlova;Noelle Kee;Josephine C. McGowan;Christine Ann Denny
  • 通讯作者:
    Christine Ann Denny

Christine Ann Denny的其他文献

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{{ truncateString('Christine Ann Denny', 18)}}的其他基金

Identifying the neural ensembles mediating fear generalization during adolescence
识别青春期介导恐惧泛化的神经系统
  • 批准号:
    10648352
  • 财政年份:
    2023
  • 资助金额:
    $ 75.82万
  • 项目类别:
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:
    10018072
  • 财政年份:
    2019
  • 资助金额:
    $ 75.82万
  • 项目类别:
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:
    9790044
  • 财政年份:
    2019
  • 资助金额:
    $ 75.82万
  • 项目类别:
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:
    10254286
  • 财政年份:
    2019
  • 资助金额:
    $ 75.82万
  • 项目类别:
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:
    10475683
  • 财政年份:
    2019
  • 资助金额:
    $ 75.82万
  • 项目类别:
Identification and manipulation of the neural ensembles mediating sundowning in an Alzheimer's disease mouse model
阿尔茨海默病小鼠模型中介导日落的神经群的识别和操作
  • 批准号:
    10016163
  • 财政年份:
    2019
  • 资助金额:
    $ 75.82万
  • 项目类别:
Optogenetic dissection of hippocampal circuitry underlying Alzheimers disease
阿尔茨海默病海马回路的光遗传学解剖
  • 批准号:
    9135544
  • 财政年份:
    2014
  • 资助金额:
    $ 75.82万
  • 项目类别:
Optogenetic dissection of hippocampal circuitry underlying Alzheimers disease
阿尔茨海默病海马回路的光遗传学解剖
  • 批准号:
    8921853
  • 财政年份:
    2014
  • 资助金额:
    $ 75.82万
  • 项目类别:
Optogenetic dissection of hippocampal circuitry underlying Alzheimers disease
阿尔茨海默病海马回路的光遗传学解剖
  • 批准号:
    8917731
  • 财政年份:
    2014
  • 资助金额:
    $ 75.82万
  • 项目类别:
Optogenetic dissection of hippocampal circuitry underlying Alzheimers disease
阿尔茨海默病海马回路的光遗传学解剖
  • 批准号:
    9354198
  • 财政年份:
    2014
  • 资助金额:
    $ 75.82万
  • 项目类别:

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THE GENETICS AND FUNCTIONAL NEUROANATOMY OF AGE-ASSOCIATED MEMORY IMPAIRMENT
年龄相关记忆障碍的遗传学和功能神经解剖学
  • 批准号:
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THE GENETICS AND FUNCTIONAL NEUROANATOMY OF AGE-ASSOCIATED MEMORY IMPAIRMENT
年龄相关记忆障碍的遗传学和功能神经解剖学
  • 批准号:
    7205360
  • 财政年份:
    2004
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CITICOLINE AND AGE ASSOCIATED MEMORY IMPAIRMENT
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  • 批准号:
    6305687
  • 财政年份:
    1999
  • 资助金额:
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CITICOLINE AND AGE ASSOCIATED MEMORY IMPAIRMENT
胞二磷胆碱与年龄相关的记忆障碍
  • 批准号:
    6115572
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    1998
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年龄相关记忆障碍(AAMI)生物学特征的研究。
  • 批准号:
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  • 财政年份:
    1997
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    $ 75.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C).
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胞二磷胆碱与年龄相关的记忆障碍
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  • 批准号:
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  • 财政年份:
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