Subcellular calcium signaling in ferret visual cortical astrocytes

项目摘要 星形胶质细胞是神经回路的主要组成部分，占灰质细胞的近三分之一。他们 通过与神经元的双向信号传导与神经电路元件在物理上和功能上相互作用。 星形胶质细胞对神经活动的反应在很大程度上是通过在多个空间和空间上增加细胞内钙来实现的。 时间尺度，通过各种机制。这些钙信号是信号传导的必要组成部分， 许多形式的星形胶质细胞信号传导回神经元的途径。因此，了解的功能作用， 星形胶质细胞在神经回路功能中的作用需要对空间和时间神经活动的定量阐明 在星形胶质细胞中引发钙信号的模式，以及亚细胞钙信号在星形胶质细胞中的整合， 单个星形胶质细胞。我们建议利用精确的神经回路来定义这些关系 视觉皮层中的组织。雪貂的视觉皮层在功能上被组织成精确的方向柱， 使得视觉刺激的不同取向在神经回路中产生空间上不同的活动模式， 这使得能够对神经活动的空间模式进行精确的实验控制。我们将特别针对 1)星形胶质细胞对不同刺激方向反应的亚细胞区室化，2） 在精确控制刺激幅度和持续时间下的反应的亚细胞组织; 3）影响 不同大脑状态下不同的神经活动模式对星形胶质细胞钙反应的影响。一起 这些研究将提供前所未有的定量洞察1）神经活动的空间模式， 激活星形胶质细胞钙信号所需，2）神经活动幅度的时间整合 这是激活星形胶质细胞钙信号所必需的，3）大脑状态促进星形胶质细胞 对神经活动的反应。这些规则的定量定义将提供一个重要的基线， 比较和测试星形胶质细胞在与疾病相关的病理状态的脑功能障碍中的作用 精神健康的问题。

Project Summary Astrocytes are major constituents of neural circuits, comprising nearly one third of cells in gray matter. They interact with neural circuit elements both physically and functionally via bidirectional signaling with neurons. Astrocytes respond to neural activity in large part by increasing intracellular calcium on multiple spatial and temporal scales, via a variety of mechanisms. These calcium signals are a necessary component of the signaling pathway for many forms of astrocyte signaling back to neurons. Thus, an understanding of the functional role of astrocytes in neural circuit function requires a quantitative elucidation of the spatial and temporal neural activity patterns that elicit calcium signaling in astrocytes, and the integration of subcellular calcium signals within individual astrocytes. We propose to define these relationships by making use of the precise neural circuit organization in ferret visual cortex. Ferret visual cortex is functionally organized into precise orientation columns, such that different orientations of visual stimulation produce spatially distinct activity patterns in neural circuits, which enables precise experimental control of the spatial patterns of neural activity. We will specifically address 1) the subcellular compartmentalization of astrocyte responses to different stimulus orientations, 2) the subcellular organization of responses under precise control of stimulus amplitude and duration and 3) the impact of the different neural activity patterns underlying different brain states on astrocyte calcium responses. Together these studies will provide unprecedented quantitative insight into 1) the spatial patterns of neural activity that are required to activate astrocyte calcium signaling, 2) the temporal integration of the magnitude of neural activity that are necessary to activate astrocyte calcium signaling and 3) the brain states that promote astrocyte responses to neural activity. Quantitative definitions of these rules will provide an important baseline against which to compare and test the role of astrocytes in the brain dysfunction of pathological states related to diseases of mental health.