CRCNS: Theory-guided studies of cortical mechanisms of multi-input integration

CRCNS:多输入整合皮质机制的理论指导研究

基本信息

  • 批准号:
    9765321
  • 负责人:
  • 金额:
    $ 39.68万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-01 至 2021-08-31
  • 项目状态:
    已结题

项目摘要

A fundamental goal for understanding the brain and mammalian and human intelligence, and to understand how processing goes awry in genetic and developmental diseases, is to understand the principles of operation of cerebral cortex. A key step is to understand "canonical" operations carried out by cortex. Here we will explore the operations of cortical circuitry in experiments guided by a new theory of a candidate canonical circuit operation. Sensory cortex must globally integrate localized sensory input to parse objects and support perception. In individual neurons, this manifests as modulation of responses to local stimuli by context or top-down influences such as attention and as interactions between local stimuli in driving responses ("normalization"). These interactions tend to be suppressive for stronger stimuli but more weakly suppressive or facilitative for weaker stimuli. Recent theoretical work in Dr. Miller's lab has proposed a novel cortical circuit motif, the stabilized supralinear network (SSN), that provides a simple unified explanation for a wide variety of neural responses related to global integration. The model serves as a guide for new experimental explorations of cortical circuitry in Dr. Van Hooser's laboratory, using both traditional experimental recording techniques and his recently developed novel optical methods for manipulating cortical activity with high spatial and temporal resolution. The SSN model, if successful, will be elaborated to best explain experimental results. In Aim 1, the light-activated channel channelrhodopsin2 (ChR2) and an optical stimulation system are used to drive activity of cortical circuits in precise spatial and temporal patterns to test the contribution of cortical circuits to normalization and contextual modulation including various SSN predictions about them. In Aim 2, the balance of drive to excitatory (E) vs. inhibitory (I) cells within the cortex will be altered using viruses that largely restrict expression of ChR2 to E or I cells. This will test SSN model predictions involving modulation of network gain by modulatory input biased toward E or I cells, mechanisms of attentional modulation, and the dependence of a "paradoxical" result -­ adding drive to I cells reduces steady-state I responses -- on the spatial pattern of drive to I cells and level of cortical activation. RELEVANCE (See instructions): We will test the predictions of a powerful framework for understanding how sensory cortex globally integrates multiple sources of input, bottom-up and top-down, to produce neuronal responses and ultimately perception. Understanding circuit changes that cause breakdown of this cortical operation may provide insight into disorders such as autism and schizophrenia, which show deficits in contextual or global processing. Understanding global integration will be necessary for the creation of prosthetic devices to treat blindness and other disorders.
理解大脑、哺乳动物和人类智能的一个基本目标, 基因和发育疾病的处理过程是如何出错的, 大脑皮层手术关键的一步是理解皮层执行的“规范”操作。这里 我们将在一个新的候选人理论指导下, 规范电路操作。感觉皮质必须全局整合局部感觉输入来解析物体 支持感知。在单个神经元中,这表现为对局部刺激的反应的调制, 背景或自上而下的影响,如注意力和驾驶中局部刺激之间的相互作用 标准化(normalization)。这些相互作用往往是抑制较强的刺激,但更弱 对较弱的刺激具有抑制或促进作用。米勒博士实验室最近的理论工作提出了一种 一种新的皮层电路基序,稳定的超线性网络(SSN),提供了一个简单的统一 解释了与全球整合有关的各种神经反应。该模型作为一个 在货车Hooser博士的实验室中,使用两种方法对皮层电路进行新的实验探索的指南 传统的实验记录技术和他最近开发的新的光学方法, 以高空间和时间分辨率操纵皮层活动。SSN模式如果成功, 这是为了更好地解释实验结果。在目标1中,光激活通道通道视紫红质2 (ChR 2)和光学刺激系统被用于在精确的空间和视觉上驱动皮层回路的活动。 测试皮层回路对正常化和上下文调制的贡献的时间模式 包括各种SSN预测。在目标2中,兴奋性(E)与抑制性(E)的驱动平衡 (I)皮质内的细胞将被病毒改变,该病毒将ChR 2的表达主要限制在E或I细胞。 这将测试SSN模型预测,包括通过调制输入偏置调制网络增益 对E或I细胞,注意力调节的机制,以及一个“矛盾”的结果的依赖性- 对I细胞增加驱动减少稳态I反应--关于I细胞驱动的空间模式和水平 大脑皮层的激活 相关性(参见说明): 我们将测试一个强大的框架的预测,以了解全球感觉皮层如何 整合多个输入源,自下而上和自上而下,以产生神经元反应, 最后是感知。了解导致这种皮层操作崩溃的电路变化可能会 提供对自闭症和精神分裂症等疾病的深入了解,这些疾病在上下文或全局方面表现出缺陷, 处理.了解全球一体化将是必要的创造假体设备,以治疗 失明和其他疾病。

项目成果

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KENNETH D MILLER其他文献

KENNETH D MILLER的其他文献

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{{ truncateString('KENNETH D MILLER', 18)}}的其他基金

Modeling V1 circuit dynamics
V1 电路动力学建模
  • 批准号:
    10231004
  • 财政年份:
    2018
  • 资助金额:
    $ 39.68万
  • 项目类别:
Modeling V1 circuit dynamics
V1 电路动力学建模
  • 批准号:
    10438693
  • 财政年份:
    2018
  • 资助金额:
    $ 39.68万
  • 项目类别:
Understanding V1 circuit dynamics and computations
了解 V1 电路动力学和计算
  • 批准号:
    10230997
  • 财政年份:
    2018
  • 资助金额:
    $ 39.68万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10230998
  • 财政年份:
    2018
  • 资助金额:
    $ 39.68万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10438688
  • 财政年份:
    2018
  • 资助金额:
    $ 39.68万
  • 项目类别:
Understanding V1 circuit dynamics and computations
了解 V1 电路动力学和计算
  • 批准号:
    10438687
  • 财政年份:
    2018
  • 资助金额:
    $ 39.68万
  • 项目类别:
TOOLS FOR ACQUISITION AND ANALYSIS OF MANY CELLULAR DATA
用于采集和分析多种细胞数据的工具
  • 批准号:
    2272783
  • 财政年份:
    1994
  • 资助金额:
    $ 39.68万
  • 项目类别:
MODELS OF CORRELATION BASED NEURAL DEVELOPMENT
基于相关性的神经发育模型
  • 批准号:
    2165225
  • 财政年份:
    1994
  • 资助金额:
    $ 39.68万
  • 项目类别:
TOOLS FOR ACQUISITION AND ANALYSIS OF MANY CELLULAR DATA
用于采集和分析多种细胞数据的工具
  • 批准号:
    2037905
  • 财政年份:
    1994
  • 资助金额:
    $ 39.68万
  • 项目类别:
TOOLS FOR ACQUISITION AND ANALYSIS OF MANY CELLULAR DATA
用于采集和分析多种细胞数据的工具
  • 批准号:
    2609675
  • 财政年份:
    1994
  • 资助金额:
    $ 39.68万
  • 项目类别:

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以额叶功能为中心的汽车驾驶能力评价方法的建立及其在事故预测中的应用
  • 批准号:
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    25330237
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    2013
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    23591741
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