Cytoskeletal Regulation of Postsynaptic Structures and Functions

突触后结构和功能的细胞骨架调节

• 批准号: 8733291
• 负责人: CHERYL F DREYFUS
• 金额: $ 27.46万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-03 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8733291
• 关键词: AMPA Receptors; Actins; Area; Brain; Brain-Derived Neurotrophic Factor; Cell physiology; Cells; Cellular Structures; Collaborations; Commit; Communication; Cues; Data; Dendritic Spines; Development; Disease; Equilibrium; Event; Excitatory Synapse; Foundations; Growth; Growth Cones; Image; Instruction; Knowledge; LIM Domain Kinase 1; LIMK1 gene; Learning; Life; Light; Long-Term Potentiation; Manuscripts; Mediating; Membrane; Memory; Mental Depression; Messenger RNA; Microtubules; Modification; Molecular; Morphology; Nervous system structure; Neurons; Neurotransmitter Receptor; Pattern; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Physiological; Plastics; Play; Presynaptic Terminals; Property; Protein Biosynthesis; Proteins; Publishing; Recombinants; Regulation; Research; Research Project Grants; Resolution; Role; Site; Slice; Stimulus; Structure; Surface; Synapses; Synaptic plasticity; Testing; Time; Translations; Universities; Vertebral column; Work; cell motility; cofilin; experience; extracellular; migration; neuronal circuitry; neurotrophic factor; novel; polymerization; postsynaptic; presynaptic; programs; receptor; relating to nervous system; research study; scaffold; spatiotemporal; trafficking

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 in association with the plasticity. The underlying cellular mechanisms that control and regulate these rapid changes in postsynaptic receptors and spine structures remain to be fully elucidated. In this proposed project, we plan to investigate the cytoskeletal mechanisms that regulate postsynaptic dynamics and plasticity. We hypothesize that the actin eytoskeleton controls spine dynamics and receptor trafficking at the postsynaptic site and MTs contribute to spine development. We will take advantage of our imaging expertise and experience in studying cytoskeletal dynamics in cultured neurons and organotypic slices to understand the cytoskeletal regulation of postsynaptic structures and functions. Three specific aims are proposed: (1) Cytoskeletal regulation of spine plasticity (2) ADF/cofilin in spine dynamics and receptor trafficking during plasticity (3) Local synthesis and degradation of actin-associated proteins during plasticity.

突触代表神经元通讯的基本单位，由成对的前突触和突触组成。 突触后末梢。大多数兴奋性突触位于树突棘上，树突棘是树突的一种 承载神经递质受体和其他突触后特化的突起。突触是 可塑性，并在神经元的发育细化过程中经历短期和长期的修改 电路以及学习和记忆过程中。突触修饰涉及突触前和突触后 变化。在突触后位点，定向神经递质受体往返的运输 膜表面被认为是长时程增强（LTP）的关键事件， 抑郁症（LTD）。此外，树突棘的形态发生快速变化 与可塑性的关系。控制和调节这些快速变化的潜在细胞机制 突触后受体和脊柱结构的变化仍有待充分阐明。在这个提议中 项目中，我们计划研究调节突触后动力学的细胞骨架机制和 可塑性。我们假设肌动蛋白细胞骨架控制脊柱动力学和受体运输 突触后位点和 MT 有助于脊柱发育。我们将利用我们的成像 研究培养神经元和器官切片的细胞骨架动力学的专业知识和经验 了解突触后结构和功能的细胞骨架调节。三个具体目标是 提出：(1) 脊柱可塑性的细胞骨架调节 (2) ADF/cofilin 在脊柱动力学和受体中的作用 可塑性期间的运输 (3) 可塑性期间肌动蛋白相关蛋白的局部合成和降解。