ASTROCYTE-NEURONAL INTERACTIONS IN THE VISUAL CORTEX

视觉皮层星形胶质细胞与神经元的相互作用

• 批准号: 8206491
• 负责人: Ken Douglas McCarthy
• 金额: $ 45.13万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206491
• 关键词: Animals; Area; Astrocytes; Behavior; Behavioral; Biological Models; Blood Vessels; Blood flow; Brain; Calcium; Calcium Signaling; Cells; Chelating Agents; Clinical; Coupled; Development; Disease; Engineering; Exhibits; G-Protein-Coupled Receptors; Genetically Engineered Mouse; Genets; Hippocampus (Brain); Hyperemia; Image; In Situ; In Vitro; Knock-out; Laboratories; Lateral Geniculate Body; Lead; Life; Light; Link; Maintenance; Measurable; Microglia; Modeling; Mus; Neurons; Neurotransmitter Receptor; Ocular Dominance; Oligodendroglia; Pathway interactions; Physiology; Play; Process; Relative (related person); Reporting; Research Personnel; Role; Sensory; Signal Transduction; Slice; Spinal Cord; Synapses; Synaptic Transmission; Synaptic plasticity; System; Testing; Vision; Vision Disorders; Visual; Visual Cortex; Visual Pathways; Visual system structure; abstracting; area striata; caged molecule; cell type; experience; functional outcomes; human CCR10 protein; in vivo; novel therapeutics; relating to nervous system; release of sequestered calcium ion into cytoplasm; response; sensory stimulus

ABSTRACT Astrocytes are the predominate cell type in brain, closely associate with all other neural cell types, exhibit a wide array of neurotransmitter receptors, respond to neuronal activity, and release neuroactive molecules; in spite of this, we know very little about the role of these cells in physiology, behavior, or disease. A major limitation in this area is the lack of models that permit the study of astrocyte function in neural systems following sensory stimulation in living animals. To date, nearly all studies of astrocytic function have relied on pharmacological approaches to activate or inactivate signaling in these cells and to record the effects of their activity on surrounding cells in vitro or in situ. It is our view that progress in this area requires a model system where: 1) sensory input in living animals can be used to activate astrocytic signaling and, 2) behavioral readouts are available for determining the functional outcome of astrocytic signaling in vivo. To this end, we propose to use the mouse central visual pathway to investigate the role of astrocytic signaling cascades in synaptic transmission and plasticity as well as in vision. In Specific Aim 1 we will use well-characterized slices of primary visual cortex to examine the pathways and mechanisms regulating astrocytic signaling in situ. In Specific Aim 2 we will use in vivo imaging to determine if astrocytic calcium responses are spatially-restricted and important in the local control of vascular tone. In Specific Aim 3 we will use in vivo imaging and genetically- modified mice to investigate the role of astrocytes in visual plasticity. Finally, in Specific Aim 4 we will genet- ically engineered mice to investigate the role of astrocytes in vision, a behavioral readout of sensory input into the visual cortex. Overall, the results of these studies should clarify the conditions where sensory input leads to the activation of astrocytic signaling and the role of astrocytic signaling in synaptic transmission and vision.

抽象的 星形胶质细胞是大脑中的主要细胞类型，与所有其他神经细胞类型密切相关，表现出 广泛的神经递质受体，对神经元活动做出反应，并释放神经活性分子；在 尽管如此，我们对这些细胞在生理、行为或疾病中的作用知之甚少。一个专业 该领域的局限性是缺乏允许研究神经系统中星形胶质细胞功能的模型 对活体动物进行感官刺激后。迄今为止，几乎所有星形胶质细胞功能的研究都依赖于 激活或灭活这些细胞中的信号传导并记录其作用的药理学方法 体外或原位对周围细胞的活性。我们认为，这一领域的进步需要一个模型系统 其中：1) 活体动物的感觉输入可用于激活星形胶质细胞信号传导，2) 行为 读数可用于确定体内星形细胞信号传导的功能结果。为此，我们 提议使用小鼠中央视觉通路来研究星形胶质细胞信号级联在 突触传递和可塑性以及视觉。在特定目标 1 中，我们将使用特征良好的切片 初级视觉皮层以检查原位星形胶质细胞信号传导的途径和机制。在 具体目标 2 我们将使用体内成像来确定星形胶质细胞的钙反应是否受到空间限制 对血管张力的局部控制很重要。在特定目标 3 中，我们将使用体内成像和遗传- 改造小鼠以研究星形胶质细胞在视觉可塑性中的作用。最后，在具体目标 4 中，我们将生成- 精心设计的小鼠研究星形胶质细胞在视觉中的作用，视觉是感觉输入的行为读数 视觉皮层。总的来说，这些研究的结果应该阐明感官输入导致的条件 星形细胞信号的激活以及星形细胞信号在突触传递和视觉中的作用。