Toward causal neuroscience: capture and manipulate emergent neuronal ensembles

走向因果神经科学:捕获和操纵新兴神经元群

基本信息

  • 批准号:
    8743303
  • 负责人:
  • 金额:
    $ 78.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-09-26 至 2018-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): It is hypothesized that animals' perceptual, emotional, or behavioral processes are governed/caused by specific patterns of brain activities, or firings of selected populations (ensembles) of neurons across multiple regions in the nervous system. Indeed recent advancements in optic imaging and multi-electrode recording technology have begun to reveal the inordinately complex dynamics of large populations of neurons in awake, behaving vertebrates such as larval zebrafish and rodents. However, these visualization/recording experiments could not definitively establish the causal relationships between the activities of neuronal ensembles and their functions. A toolkit that enables neuroscientists to be not only observers, but also actuators of the observed ensembles is critically needed for "causal neuroscience". The difficulty to developing such a toolkit lies in th complexity of the mammalian brain, which contains billions of neurons and trillions of synapses. Thus, individual neurons are likely to participate in different active ensembles at different time points. Hence the ensembles associated with a given behavioral or perceptual process are emergent properties arising out of the complicated interactions among millions of neurons. Therefore, ensembles are unlikely to be genetically pre-determined, and molecule or cell-type based methods are not useful for "labeling and manipulating" them. To overcome this difficulty, we will develop a novel toolkit consisting of two key components: (1) a mouse line designed to express, transiently and selectively, a very unstable foreign receptor only in activated neurons, and (2) engineered non-toxic, pseudo-typed viruses that can only infect neurons expressing this foreign receptor. In this way, timed-injection of the pseudo-typed viruses will allow us to specifically and permanently “capture” the recently activated ensembles (which are the ones expressing the viral receptor). The engineered viruses can introduce any desired genes, including optogenetic, chemical-genetic and other molecular tools into the ensembles for subsequent functional studies and manipulations. We plan to carry out proof-of-principle experiments to test the broad applicability of this toolkit for examining the emergence and evolution of neuronal ensembles, and for dissecting the connectivity, electrophysiological properties, learning-induced changes, and causal functions of the emergent ensembles using selected mouse behavioral paradigms. Successful development of this toolkit should transform “causal neuroscience” and open the gateways for understanding the true functional underpinnings of learning, memory, perception, emotion, and many subconscious processes.
描述(由申请人提供):假设动物的感知、情感或行为过程是由特定的大脑活动模式或大脑活动的激发所支配/引起的。 神经系统中跨多个区域的神经元的选定群体(集合)。事实上,光学成像和多电极记录技术的最新进展已经开始揭示清醒的行为脊椎动物(如斑马鱼和啮齿动物)中大量神经元的异常复杂动力学。然而,这些可视化/记录实验不能明确地建立神经元集合的活动和它们的功能之间的因果关系。“因果神经科学”迫切需要一个工具包,使神经科学家不仅是观察者,而且是所观察到的整体的执行器。开发这样一个工具包的困难在于哺乳动物大脑的复杂性,它包含数十亿个神经元和数万亿个突触。因此,单个神经元可能在不同的时间点参与不同的活动集合。因此,与给定的行为或感知过程相关的集合是从数百万神经元之间复杂的相互作用中产生的涌现特性。因此,集合不太可能是遗传预先确定的,并且基于分子或细胞类型的方法对于“标记和操纵”它们是无用的。为了克服这一困难,我们将开发一种新的工具包,包括两个关键组件:(1)一种小鼠系,旨在瞬时和选择性地表达一种仅在激活的神经元中非常不稳定的外源受体,以及(2)工程无毒的假型病毒,只能感染表达这种外源受体的神经元。这样,假型病毒的定时注入将 允许我们专门和永久地“捕捉”最近激活的合奏(这是那些 表达病毒受体)。工程病毒可以引入任何所需的基因,包括 光遗传学,化学遗传学和其他分子工具到合奏,为随后的功能 研究和操作。我们计划进行原理验证实验,以测试广泛的适用性 这个工具包的出现和进化的神经元合奏,并解剖 连接性,电生理学特性,学习引起的变化,以及因果函数的 紧急合奏使用选定的小鼠行为范例。成功开发该工具包 应该转变“因果神经科学”,并打开理解真正功能的大门。 学习、记忆、感知、情感和许多潜意识过程的基础。

项目成果

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Fan Wang其他文献

Fan Wang的其他文献

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{{ truncateString('Fan Wang', 18)}}的其他基金

Unraveling the Neural Bases of Body Schema
揭开身体图式的神经基础
  • 批准号:
    10696706
  • 财政年份:
    2023
  • 资助金额:
    $ 78.5万
  • 项目类别:
Defining Brainstem Neuronal Pathways for Orofacial Motor Actions
定义口面部运动动作的脑干神经元通路
  • 批准号:
    10413914
  • 财政年份:
    2018
  • 资助金额:
    $ 78.5万
  • 项目类别:
Defining Brainstem Neuronal Pathways for Orofacial Motor Actions
定义口面部运动动作的脑干神经元通路
  • 批准号:
    10199074
  • 财政年份:
    2018
  • 资助金额:
    $ 78.5万
  • 项目类别:
Functions of distinct trigeminal brainstem projection pathways in tactile behavior
不同三叉神经脑干投射通路在触觉行为中的功能
  • 批准号:
    9298006
  • 财政年份:
    2017
  • 资助金额:
    $ 78.5万
  • 项目类别:
Pre-motor Neural Circuits for Exploratory Movement
用于探索性运动的前运动神经回路
  • 批准号:
    8617309
  • 财政年份:
    2013
  • 资助金额:
    $ 78.5万
  • 项目类别:
Toward causal neuroscience: capture and manipulate emergent neuronal ensembles
走向因果神经科学:捕获和操纵新兴神经元群
  • 批准号:
    8559171
  • 财政年份:
    2013
  • 资助金额:
    $ 78.5万
  • 项目类别:
Pre-motor Neural Circuits for Exploratory Movement
用于探索性运动的前运动神经回路
  • 批准号:
    10348340
  • 财政年份:
    2013
  • 资助金额:
    $ 78.5万
  • 项目类别:
Pre-motor Neural Circuits for Exploratory Movement
用于探索性运动的前运动神经回路
  • 批准号:
    10204126
  • 财政年份:
    2013
  • 资助金额:
    $ 78.5万
  • 项目类别:
Pre-motor Neural Circuits for Exploratory Movement
用于探索性运动的前运动神经回路
  • 批准号:
    10438605
  • 财政年份:
    2013
  • 资助金额:
    $ 78.5万
  • 项目类别:
Pre-motor Neural Circuits for Exploratory Movement
用于探索性运动的前运动神经回路
  • 批准号:
    8503718
  • 财政年份:
    2013
  • 资助金额:
    $ 78.5万
  • 项目类别:

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