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

大脑是复杂的器官，其整体结构和功能就像一个小镇一样。大脑的组成单元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单独的建筑，把电路想象成邻居。神经元本身是多种多样和复杂的，由不同的隔间组成，称为轴突和树突--继续类比建筑中的不同房间。这些树突和轴突的任务是与其隔壁神经元形成功能性连接，从而形成回路。由于如果不很好地理解一个城镇是如何建造和相互联系的，以及每个社区和建筑扮演着什么角色(例如，有商店和市政厅的城镇中心，有房屋、学校和超市的居民区)，我们就不可能理解一个城镇是如何运作的，所以我们需要类似的对电路、神经元和它们的隔间的多层次了解，以了解大脑是如何工作的--或者它是如何失灵导致自闭症、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，建立一种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，我们将把这些小尺度的测量与大规模、所有大脑活动和整体动物行为相匹配。因此，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合成，说明一个定义的大脑电路及其组成细胞如何协同作用来控制行为，或者在病理状态下被改变。

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.