INSPIRE: Memory Storage by Variable-size Stable Structures

记忆的机制是生物学的主要奥秘之一。最近的研究表明，作为学习的结果，突触生长，突触的大小是存储记忆的组成部分。这项工作的目的是使用新开发的超分辨率显微镜直接观察脑组织中的这种生长过程，并了解为什么一旦发生学习，这种结构就会具有稳定的大小。不稳定会导致记忆的丧失，所以进化被认为是最大化稳定性的有利方式。为了深入了解稳定性的机制，将使用物理和计算模型系统。如果能够理解在可变尺寸下稳定性的原理，这项工作的结果可能会打开纳米技术新时代的大门，在纳米技术中可以利用这些原理，从而可能为自组装问题提供新的解决方案。该项目的其他贡献包括为来自科学和技术代表不足的群体的学生组织和教授科学编程语言MATLAB的课程，以及为美国受训人员提供参加国际合作的机会。该提案关注的是没有固定尺寸但可以以多种不同尺寸存在的超分子结构，所有这些结构都是稳定的。因此，如果刺激导致从一个稳定状态到另一个稳定状态的转变，则该结构具有信息存储能力（记忆）。研究人员将这种结构称为变尺寸稳定结构（VSSS）。对VSSS的兴趣来自两个看似无关的领域：神经科学和纳米结构物理学。记忆的分子基础是神经科学中最基本的未解决的问题之一。证据有力地表明，突触的生长是为了编码记忆。因此，大脑中的记忆存储似乎是一个结构性问题，需要努力理解使记忆存储成为可能的结构原则。该项目将尖端光学显微镜与理论建模相结合。利用一种新的超分辨率显微镜，研究人员将首次努力在真实的时间内观察突触可塑性过程中的突触生长。理论工作的目标是发展VSSS的物理理论，并评估不同的模型，包括从突触研究中出现的模型。要解决的问题包括：（一）多个组件之间的合作互动的重要性，以产生稳定的，但动力学上可访问和可重构的组装。(ii)导致自终止组装的设计原则，例如通过有限尺寸模块的增长。(iii)非平衡能量消耗改变VSSS极限的机制。一个最终的目标是一个广义的非平衡自组装理论能够描述VSSS。该项目由综合有机系统部门的神经系统集群和物理部门的生命系统计划物理共同资助。

The mechanism of memory is one the major mysteries of biology. Recent work suggests that as a result of learning synapses grow and that the size of the synapse is what stores the components of memories. The aim of the proposed work is to visualize directly this growth process in brain tissue using a newly developed super-resolution microscope, and to understand why such structures have stable size once learning has occurred. Instability would result is loss of memory, so evolution is thought to have favored ways of maximizing stability. To gain insight into the mechanism of stability, physical and computational model systems will be used. If the principles that underlie stability in the face of variable size can be understood, the outcome of this work could open the door to a new era in nanotechnology in which these principles could be utilized, leading potentially to novel solutions to problems in self-assembly. Additional contributions of this project include the organization and instruction of a course in the scientific programming language, MATLAB, in an enrichment course for students from groups under-represented in science and technology, and the opportunity for US trainees to participate in an international collaboration. This proposal focuses on supramolecular structures that do not have fixed size but can exist in multiple different sizes, all of which are stable. Thus, if a stimulus causes the transition from one stable state to another, the structure has information storage capability (memory). The investigators termed this type of structure variable-size stable structures (VSSS). Interest in VSSS arises from two seemingly unrelated fields: neuroscience and the physics of nanostructures. The molecular basis of memory is one the most fundamental unsolved problems in neuroscience. Evidence strongly suggests that synapses grow to encode memory. Thus, memory storage in the brain appears to be a structural problem, and efforts need to be made to understand the structural principles that make memory storage possible. The project integrates cutting-edge optical microscopy with theoretical modeling. Utilizing a newly-available super-resolution microscope, the investigators will make the first effort to observe synaptic growth during synaptic plasticity in real time. The goal of the theoretical efforts is to develop a physical theory of VSSS and evaluate different models, including ones that have emerged from the study of synapses. Questions to be addressed include: (i) The importance of cooperative interactions among multiple components to generating stable yet kinetically accessible and reconfigurable assemblages. (ii) Design principles that lead to self-terminating assembly, such as growth by finite-size modules. (iii) Mechanisms by which nonequilibrium energy consumption changes the limits of VSSS. An ultimate goal is a generalized theory for nonequilibrium self-assembly capable of describing VSSS. This project is jointly funded by the Neural Systems Cluster in the Division of Integrative Organismal Systems and by the Physics of Living Systems Program in the Physics Division.