Memory molecules and where to find them - does our brain store memories in binary format?

这个项目将测试一个关于记忆如何储存在大脑中的新理论。我们已经确定了一个以前未被认识到的，扩展的机械二进制开关网络，这些开关内置于每个突触中，从而导致提出了记忆机械基础的MeshCODE理论。我们最近发现塔林是支撑每个突触的蛋白质网络的重要组成部分，它是一种能够以二进制格式存储信息的记忆分子，并写入其13个二进制开关的形状中。我们假设在突触信号传导之后，神经元细胞骨架短暂而精确地收缩，这改变了这些记忆分子中的开关模式，这些记忆分子动态地控制突触活动和通过神经元回路的信息流。这个项目的目的是确定这种变化发生在神经元活动的突触支架。我们预测，talin上张力的变化将为可视化提供二进制编码被改变时的指纹，该项目（Goult Lab）将开发探针和工具来可视化talin在体内何时何地改变形状。然后，学生将使用这些工具来寻找神经元（Staras实验室）中的二进制代码更新，使用已建立的突触活动读数。这将使我们能够确定允许突触调整其突触强度的基本机制，利用该领域最新的技术。该项目将为学生提供结构机械生物学（肯特）的尖端多学科培训，以及突触功能的细胞测定和神经科学（苏塞克斯），以测试突触信号以编码信息的方式驱动记忆分子变化的假设。影响：这个项目的成功完成将定义有机计算的规则，并为信息如何在大脑中存储和处理建立一个新的范式。

This project will test a novel theory for how memories might be stored in the brain. We have identified a previously unrecognised, expansive network of mechanical binary switches that are built into each and every synapse, leading to the proposed MeshCODE theory of a mechanical basis of memory. We recently discovered how talin, an essential component of the protein meshwork that scaffolds each synapse, is a memory molecule able to store information in a binary format, written into the shapes of its 13 binary switches. We hypothesise that following synaptic signalling, the neuronalcytoskeleton contracts briefly and precisely which alters the switch patterns in these memory molecules which dynamically controls synaptic activity and the flow of information through neuronal circuits. This project aims to establish that such changes occur in the synaptic scaffolds during neuronal activity. We predict that a change in tension on talin will provide a fingerprint for visualising when the binary coding is being altered and the project (Goult Lab) will develop probes and tools to visualise when, and where, talin changes shape in vivo. These tools will then be used by the student to look for binary code updating in neurons (Staras Lab) using established readouts of synaptic activity. Together this will enable us to identify the fundamental mechanisms that allow synapses to adjust their synaptic strength, exploiting the most current technologies in the field. This project will provide the student with a cutting-edge multidisciplinary training in structural mechanobiology (Kent) with cellular assays and neuroscience of synapse function (Sussex) to test the hypothesis that synaptic signalling drives changes in the memory molecules in a way that encodes information. Impact: Successful completion of this project will define the rules of organic computation and establish a new paradigm for how information is stored and processed in the brain.