Matching molecules, cells and behaviour to understand brain function and disorder

匹配分子、细胞和行为以了解大脑功能和紊乱

• 批准号: MR/X012271/1
• 负责人: Jasper Poort
• 金额: $ 38.25万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX012271%2F1
• 关键词: Matching; molecules; cells; behaviour; understand

Brains are complex organs whose overall structure and functioning resembles that of a small town. The brain's building blocks are specialized cells called neurons arranged in discrete circuits. We can think of neurons as individual buildings, and circuits as neighbourhoods. Neurons are themselves varied and complex, and made up of various compartments, called axons and dendrites - different rooms in the building, to continue the analogy. These dendrites and axons are tasked with the key role of forming functional connections with their next-door neurons, thus forming a circuit. As it is not possible to understand how a town functions without having a good understanding of how it is built and interconnected, and which role each neighbourhood and building serves (e.g. town centre with shops and city hall, residential areas with houses, schools and supermarkets), we need similar multi-level understanding of circuits, neurons and their compartments to understand how brains work - or how it misfires causing disorders such as autism, schizophrenia, anxiety. In order to achieve this multi-level analytical approach, we will use rodents as animal models and build an experimental apparatus capable of simultaneously measuring structure, function and connectivity of neurons and circuits, and we will match these small-scale measures with large-scale, all brain activity and overall animal behaviour. By integrating these town-to-room approaches, we thus aim to provide a multi-level synthesis of how a defined brain circuits and their constituent cells function in synergy to control behaviour, or are altered in pathological states.

大脑是复杂的器官，其整体结构和功能类似于一个小镇。大脑的组成部分是被称为神经元的特殊细胞，它们排列在离散的电路中。我们可以把神经元想象成独立的建筑，把电路想象成社区。神经元本身是多样而复杂的，由不同的隔间组成，被称为轴突和树突——继续这个类比，它们是建筑物中的不同房间。这些树突和轴突的任务是与相邻的神经元形成功能性连接，从而形成一个回路。如果不很好地了解城镇是如何建造和相互联系的，以及每个社区和建筑的作用（例如，城镇中心有商店和市政厅，住宅区有房子、学校和超市），就不可能理解城镇的功能，我们需要对电路、神经元及其隔层有类似的多层次理解，以了解大脑是如何工作的，或者它是如何失火导致自闭症、精神分裂症、焦虑等疾病的。为了实现这种多层次的分析方法，我们将以啮齿动物为动物模型，建立一个能够同时测量神经元和电路的结构、功能和连通性的实验装置，并将这些小规模的测量与大规模的、所有的大脑活动和整体动物行为相匹配。通过整合这些从城镇到房间的方法，我们的目标是提供一个多层次的综合，了解一个确定的脑回路及其组成细胞如何协同作用来控制行为，或在病理状态下被改变。