Cytoskeletal Regulation of Postsynaptic Structures and Functions

突触代表神经元交流的基本单位，由成对的前额和前额叶组成。 突触后终末。大多数兴奋性突触位于树突上，树突棘是树突的一种。 神经递质受体和其他突触后特化的突起。突触是 并在神经元发育精化过程中进行短期和长期的修改 电路，以及在学习和记忆过程中。突触修饰涉及突触前和突触后 改变。在突触后部位，神经递质受体直接往返于 膜表面被认为是长时程增强(LTP)和 抑郁症(有限公司)。此外，树突棘在其形态上经历了快速的变化 与可塑性有关。控制和调节这些快速反应的潜在细胞机制 突触后受体和脊椎结构的变化仍未完全阐明。在本建议中 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椎动力学和受体运输。 突触后部位和MTS对脊柱发育有贡献。我们将利用我们的成像技术 在培养神经元和器官切片中研究细胞骨架动力学的专业知识和经验 了解细胞骨架对突触后结构和功能的调节。三个具体目标是 提出：(1)细胞骨架对脊柱可塑性的调节(2)ADF/Cofilin在脊柱动力学和受体中的作用 可塑性运输(3)可塑性过程中肌动蛋白相关蛋白的局部合成和降解。

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.