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

基本信息

批准号：
8787739
负责人：
Ken Douglas McCarthy
金额：
$ 39.57万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8787739
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 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 in vivo imaging novel therapeutics relating to nervous system release of sequestered calcium ion into cytoplasm response sensory input sensory stimulus visual plasticity

项目摘要

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紧密相关，显示广泛的神经递质受体，对神经元活性反应并释放神经活性分子。在有一群，我们对这些细胞在生理，行为或疾病中的作用一无所知。专业该领域的限制是缺乏允许研究神经系统中星形胶质功能的模型在活动物中进行感官刺激。迄今为止，星形细胞功能的几乎所有研究都依赖在这些细胞中激活或灭活信号传导的药理方法并记录其影响在体外或原位对周围细胞的活性。我们认为，该领域的进展需要模型系统其中：1）可用于激活星形胶质细胞信号的感觉输入和2）行为可用于确定体内星形细胞信号传导的功能结果。为此，我们建议使用小鼠中央视觉途径研究星形细胞信号级联的作用突触传递和可塑性以及视觉。在特定目标1中，我们将使用特定的切片主要视觉皮层检查原位调节星形胶质细胞信号的途径和机制。在特定目标2我们将在体内成像中使用体内成像来确定星形细胞钙反应是否受到空间限制对于局部控制血管音调而言很重要。在特定目标3中，我们将在体内成像和遗传学上使用修饰的小鼠研究星形胶质细胞在视觉可塑性中的作用。最后，在特定目标4中，我们将基因 - Inally工程的小鼠研究星形胶质细胞在视觉中的作用，这是对感官输入的行为读数视觉皮层。总体而言，这些研究的结果应阐明感官输入导致的条件星形细胞信号传导的激活以及星形胶质细胞信号在突触传播和视觉中的作用。