Rho-family GTPases in Synaptic Plasticity

在这个应用中提出的研究涉及记忆形成和基本脑功能的分子机制。大脑中的神经细胞（神经元）通过突触相互交流，释放一种化学物质（神经递质）穿过突触，激活相邻神经元的受体。突触可以通过改变突触内神经递质受体的数量来改变它们的强度。此外，细胞靠近突触的部分（称为树突棘）的结构可以通过细胞骨架（细胞骨架）的重排而改变。这些事件发生在被称为突触可塑性的过程中，这被认为是学习和记忆形成的分子/细胞关联。在这项研究中，我们旨在进一步了解突触可塑性中发生的分子变化。我们发现，突触可塑性中神经递质受体运输的关键蛋白质与另外两种蛋白质相互作用，这两种蛋白质被认为是由各种细胞信号控制的广泛细胞过程的分子开关。我们将研究为什么这些分子开关与运输蛋白相互作用。我们认为它们对诱导大脑突触可塑性的细胞信号作出反应，并影响神经递质受体的运输，从而导致突触强度的变化。此外，这些新的相互作用可能为突触可塑性期间的耦合运输和细胞骨架变化提供了一种手段。这项工作很重要，因为它将为学习和记忆的分子机制提供丰富的新信息，这些机制在阿尔茨海默病等疾病中起作用。公众可以通过布里斯托尔神经科学（BN）访问布里斯托尔大学的神经科学研究进展。BN是一个最近成立的组织，汇集了神经科学的各个方面，特别是以促进对神经系统基本原理的理解和开发神经系统疾病和疾病的新疗法为目标。有一个广泛的网站允许公众访问我们实验室正在进行的研究。国家统计局也积极安排各种活动，例如在当地学校举办讲座和活动，以增加公众对科学的了解。

The research proposed in this application involves the molecular mechanisms of memory formation and basic brain function. Nerve cells (neurons) in the brain communicate with one another at connections called synapses, by releasing a chemical (neurotransmitter) that travels across the synapse and activates a receptor in the adjacent neuron. Synapses can change their strength by changing the number of neurotransmitter receptors in the synapse by trafficking the receptors to and from the synapse. Furthermore, the structure of the part of the cell close to the synapse (called the dendritic spine) can change by rearrangements of the cell skeleton (the cytoskeleton). These events occur in processes known as synaptic plasticity, which are thought to represent a molecular/ cellular correlate of learning and formation of memories. In this study, we aim to further the understanding of the molecular changes that occur in synaptic plasticity. We have found that a protein pivotal for neurotransmitter receptor trafficking in synaptic plasticity physically interacts with two other proteins that are known to function as molecular switches for a wide range of cellular processes that are controlled by a variety of cell signals. We will investigate why these molecular switches interact with the trafficking protein. We propose that they respond to the cell signals that induce synaptic plasticity in the brain and influence the trafficking of neurotransmitter receptors to bring about changes in synaptic strength. Furthermore, these novel interactions may provide a means for coupling trafficking and cytoskeletal changes during synaptic plasticity. This work is important because it will lead to a wealth of novel information about the molecular mechanisms of learning and memory, which malfunction in disorders such as Alzheimer s disease. The public is able to access the progress of neuroscience research in the University of Bristol via Bristol Neuroscience (BN). BN is a recently-formed organisation that brings together all aspects of neuroscience, specifically with the aim of advancing understanding of the basic principles of the nervous system and development of new treatments for neurological disorders and disease. There is an extensive website that allows the public to gain access to the research going on in our labs. BN is also active in arranging various activities such as talks at local schools and events to increase public understanding of science.