Actin Regulation of Dendritic Spine Development and Plasticity

项目摘要 化学突触由成对的突触前和突触后终末组成。最令人兴奋的 突触存在于树突棘上，这是一种树突状突起，承载着神经递质受体和 其他突触后特化。突触是可塑性的，可以进行短期和长期的修改 在神经元回路的发育过程中，以及在学习和记忆过程中。突触 修饰包括突触前和突触后的变化。在突触后部位，定向运输 往返于膜表面的神经递质受体被认为是导致长时间高血压的关键事件。 时程增强(LTP)和抑制(LTD)。此外，树突棘还经历了快速的 它们在塑性过程中的形态变化。控制和调节的潜在细胞机制 这些突触后受体和脊椎结构的快速变化仍未完全阐明。这个 细胞骨架控制着细胞结构运动性的许多方面，如果不是全部的话。细胞骨架是如何 然而，在可塑性过程中，对突触后结构、功能和修饰的调节仍然很差 明白了。这项拟议的研究旨在研究涉及局部G-肌动蛋白调节的新肌动蛋白机制 以及结构-功能耦合，使突触后结构和特化得以发展 是正常突触所必需的。具体地说，我们将研究潜在的分子机制。 脊柱G-肌动蛋白的丰富及其在脊柱发育过程中的动态调节。此外，这项研究将 肌动蛋白偶联中(+)末端封端蛋白CP与Shank支架蛋白的相互作用 基于结构变化和突触后特化的发展。考虑到这么多神经细胞 障碍与突触连接和可塑性的改变有关，我们希望获得更好的 理解突触可塑性背后的分子和细胞机制是很重要的 有助于我们了解大脑在生理和病理条件下的发育和功能。

Project Summary Chemical synapses 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 cellular structures. How the cytoskeleton regulates postsynaptic structure, function, and modifications during plasticity, however, remains poorly understood. This proposed study aims to investigate novel actin mechanisms involving local G-actin regulation and structure-function coupling that enable the development of postsynaptic structure and specialization required for a functional synapse. Specifically, we will investigate the molecular mechanism underlying the spine enrichment of G-actin and its dynamic regulation during spine development. Furthermore, the study will a novel interaction between (+) end capping protein CP and Shank scaffolding protein in coupling the actin- based structural changes and the development of the postsynaptic specialization. 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.