Actin Mechanisms of Postsynaptic Structure and Function

突触后结构和功能的肌动蛋白机制

• 批准号: 8998069
• 负责人: James Q Zheng
• 金额: $ 38.72万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8998069
• 关键词: Actins; Binding; Brain; Cell physiology; Cells; Chemical Synapse; Chemosensitization; Communication; Complex; Cytoskeleton; Data; Dendritic Spines; Development; Disease; Event; Excitatory Synapse; Exhibits; F-Actin; Filament; G Actin; Goals; Growth; Health; Image; Knowledge; Learning; Long-Term Potentiation; Membrane; Memory; Mental Depression; Microfilaments; Minus End of the Actin Filament; Modification; Molecular; Morphology; Neurons; Neurotransmitter Receptor; Optics; Pattern; Physiological; Play; Presynaptic Terminals; Protein Family; Public Health; Regulation; Role; Series; Site; Slice; Structure; Surface; Synapses; Synaptic Receptors; Synaptic plasticity; Testing; Tropomyosin; Vertebral column; Vertebrates; Work; base; cell motility; cofilin; crosslink; experience; knock-down; membrane assembly; molecular imaging; monomer; neural circuit; neuronal circuitry; novel; polymerization; postsynaptic; receptor; relating to nervous system; research study; response; scaffold; spatiotemporal; synaptogenesis; trafficking; tropomodulin

 DESCRIPTION (provided by applicant): Synapses represent the basic unit of neuronal communications and are composed of paired pre- and post- synaptic terminals. Most of the excitatory synapses reside on dendritic spines, a type of dendritic protrusion that hosts neurotransmitter receptors and other postsynaptic specializations. Synapses are plastic and undergo short- and long-term modifications during developmental refinement of neuronal circuitry, as well as during learning and memory. Synaptic modifications involve both pre- and post-synaptic changes. At the postsynaptic site, directed trafficking of neurotransmitter receptors to and from the membrane surface is believed to be a key event underlying long-term potentiation (LTP) and depression (LTD), respectively. In addition, dendritic spines undergo rapid changes in their morphology during plasticity. The underlying cellular mechanisms that control and regulate these rapid changes in postsynaptic receptors and spine structures remain to be fully elucidated. The cytoskeleton controls many, if not all, aspects of the motility of celllar structures. How the cytoskeleton regulates postsynaptic structure, function, and modifications during plasticity, however, remains poorly understood. This proposed study aims to elucidate the actin mechanisms that control spine development, dynamics, and function. We will take advantage of our imaging expertise and experience in studying cytoskeletal dynamics in cultured neurons and organotypic slices to understand the actin regulation of postsynaptic structure and function. Specifically, we will test the novel hypothesis that coordinated monomeric G-actin localization and timely end capping of actin filaments are essential for spatiotemporal actin remodeling in the spine to underlie postsynaptic modifications during plasticity. Given that many neural disorders are associated with alterations in synaptic connections and plasticity, we hope to gain a better understanding of the molecular and cellular mechanisms underlying synaptic plasticity, which is of importance to our understanding of brain development and functions under both physiological and pathological conditions.

 描述（通过应用程序证明）：突触代表神经元通信的基本单位，由配对前突触终端组成记忆基本的机制和常规的变化链结构是完全溶解的优势或成像专业知识和研究培养的神经元和器官切片中细胞骨架动力学方面的经验，以了解突触后结构和功能的八个斑点，我们将测试新的假设，即配位单体G-肌动蛋白定位，并及时地结束了时空的结局。在脊柱中重塑可在可塑性期间进行修饰。在生理和病理条件下的功能。