Mechanisms controlling the number and location of synaptic AMPARs

谷氨酸是大脑中的一种分子，负责将信息从一个神经元传递到另一个神经元。在接收神经元中，谷氨酸与被称为受体的蛋白质结合，受体激活该神经元，而受体又经常刺激该神经元释放谷氨酸，从而激活链中的下一个神经元。我们对称为AMPA受体(AMPAR)的谷氨酸受体亚型特别感兴趣。通过AMPAR传递的信息代表了大脑中绝大多数的信息流。为了正常运作，AMPAR需要精确地定位在神经元的表面。我们工作的重点是神经元如何实现在正确的时间将AMPAR送到正确的位置这一非凡的壮举。此外，AMPAR的数量和位置可以快速改变。已发现存在指导和锚定AMPAR的蛋白质；它们决定AMPAR表达的水平和位置，并连接到神经元内的特定信号通路。该项目旨在提供AMPAR如何在神经元周围运输(运输)的更完整的图景，并定义相互作用蛋白质的特定角色。我们将使用一种组合的方法，充分利用过去几年所取得的技术进步来阐明支配AMPAR翻转和表面表达的原理。为此，我们将研究在静止的、未受刺激的神经元中以及在受到生理相关刺激刺激的神经元中发生的情况。我们将使用新的显微镜和特殊的荧光蛋白标签，使我们能够实际看到AMPAR在细胞中的运动，以及不同条件如何改变这一点。然后，我们将使用生化方法来计算出哪些蛋白质参与了这些运动的协调，以及当我们阻止它们正常工作时会发生什么。公众可以通过布里斯托尔神经科学(BN)获得布里斯托尔大学的神经科学研究。有一个内容广泛的网站，允许公众访问我们实验室正在进行的研究。BN还积极安排活动，以增进公众对科学的理解。通过BN和PI提供的扩大参与计划？大脑是如何工作的？给学校的A-Level学生。

Glutamate is a molecule in the brain that transfers messages from one neurone to the next. In the receiving neurone, glutamate binds to proteins called receptors that activate that neurone which, in turn, often stimulates it to release glutamate itself to activate the next neurone in the chain. We are particularly interested in the glutamate receptor subtype called AMPA receptors (AMPARs). Information passing through AMPARs represents the vast majority of information flow in the brain. To function correctly, AMPARs need to be precisely located on the surface of the neurone. The focus of our work is how neurones achieve the remarkable feat of getting the AMPARs to the right place at the right time. In addition, the number and location of AMPARs can be rapidly changed. It has been discovered that there are proteins that direct and anchor AMPARs; they determine the level and location of AMPAR expression and they connect to specific signalling pathways inside the neurone. This project aims to provide a more complete picture of how AMPARs are transported (trafficked) around the neurone and define the specific roles of interacting proteins. We shall use a combination of methods that takes full advantage of the technological advances made over the last few years to elucidate the principles that govern the turnover and surface expression of AMPARs.To do this we will look at what happens in both resting, unstimulated neurones and also in neurones that have been stimulated with physiologically relevant stimuli. We will use new microscopes and special fluorescent protein labels that allow us to actually see AMPARs moving in the cell and how this is changed by different conditions. We will then use biochemical methods to work out what proteins are involved in orchestrating these movements and what happens when we prevent them from working properly. The public can access neuroscience research in the University of Bristol via Bristol Neuroscience (BN). 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 events to increase public understanding of science. Via BN and the widening participation scheme the PI gives talks about ?how the brain works? to A-level students in schools.