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，学习的结果是突触生长，突触的大小是存储记忆成分的东西。这项工作的目的是使用一种新开发的超分辨率显微镜直接观察大脑组织中的这种生长过程，并理解为什么这种结构在学习发生后具有稳定的大小。不稳定会导致记忆的丧失，所以进化被认为倾向于最大化稳定性的方式。为了深入了解稳定性的机制，将使用物理和计算模型系统。如果能够理解在面对可变尺寸时保持稳定性的原理，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，这些原理可以被利用，可能会导致自组装问题的新解决方案。该项目的其他贡献包括组织和指导科学编程语言MATLAB课程，为来自科学和技术领域代表性不足的群体的学生提供丰富课程，并为美国学员提供参与国际合作的机会。这一建议的重点是超分子结构，没有固定的大小，但可以存在多种不同的大小，所有这些都是稳定的。因此，如果一个刺激引起从一个稳定状态到另一个稳定状态的过渡，该结构具有信息存储能力（记忆）。研究者将这种类型的结构称为变尺寸稳定结构（VSSS）。对纳米结构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尚未解决的最基本的问题之一。证据有力地表明，突触的生长是为了对记忆进行编码。因此，记忆在大脑中的储存似乎是一个结构问题，需要努力去理解使记忆储存成为可能的结构原理。该项目将先进的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，研究人员将首次在突触可塑性过程中实时观察突触生长。理论工作的目标是发展一个物理理论的VSSS和评估不同的模型，包括那些已经从突触的研究中出现。需要解决的问题包括：(i)多个组件之间的合作相互作用对于产生稳定但动态可及和可重新配置的组合的重要性。导致自终止组装的设计原则，例如按有限尺寸的模块生长。（iii）非平衡能量消耗改变vss极限的机制。一个最终的目标是一个广义的理论，非平衡自组装能够描述VSSS。该项目由综合有机系统学部的神经系统集群和物理学部的生命系统物理项目共同资助。

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.