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Networks of neural dynamics: Knowledge-discovery for experimental neuroscience

神经动力学网络：实验神经科学的知识发现

基本信息

批准号：
MR/J008648/2
负责人：
Mark Humphries
金额：
$ 35.15万
依托单位：
University of Nottingham
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FJ008648%2F2
关键词：
Networks neural dynamics Knowledge discovery

项目摘要

What is happening in your brain when you think and act? Cells are firing tiny electrical pulses, little spikes of activity, all across the brain. Some groups of cells emit these spikes at the same time, all of them responding to sudden noise, or to the swinging of your arm. In other groups, the spikes occur in a fixed sequence across the cells, remembering the path you just took from the front door to the bus-stop. Fundamentally, the brain works by co-ordinating activity between its cells. So when cells stop being precisely co-ordinated, the brain stops working properly. In an epileptic fit, the cells across the cortex all become synchronised and waves of activity drown out the fine control of the muscles. In dementia, the loss of synchronisation between cells prevents reliable recall of past events. The goal of my research is to enable us to find and analyse the co-ordinated activity of brain cells. Neuroscientists are now able to record the spikes from hundreds of separate cells, for hours at a time, from all across the brain. Yet the resulting data mountain is growing without the ability to analyse those recordings. We have many methods for comparing the activity of two cells, but few for comparing the activity of hundreds. We have even fewer methods for finding when in each recording the co-ordination happens, or for finding which cells are taking part, or for finding if the co-ordination is made up of simultaneous spikes, a sequence of spikes, or something more complex. Without these methods, these recordings cannot reveal what co-ordinated activity of individual cells tells us about how the brain functions and dysfunctions. I will develop analysis methods that are able to take the recordings and automatically solve all these problems: finding when the cells are active together, which groups they belong to, and what form that co-ordinated activity takes. I will apply these methods to three areas of neuroscience research that seek to study the brain in health and disease by recording many cells at the same time. First, with Dr Constance Hammond's lab in Marseille, we will analyse their recordings of the developing rat striatum, a large forebrain system that is central to both the control and learning of actions. We will use my methods to understand how the co-ordinated activity in the healthy striatum develops over pregnancy and infancy, and then understand how genetic and environmental factors disrupt this correct development, leading to disorders of the striatum that appear in youth, like Tourette's syndrome. Second, with Dr Sid Wiener's lab in Paris, we will analyse their recordings from the forebrains of rats learning to solve spatial navigation tasks in mazes. We will use my methods to understand how co-ordinated activity across the forebrain develops during learning. Particularly we will analyse how the sudden onset of widespread co-ordination that precedes correct decisions on the task depends on dopamine, and how replays of co-ordinated activity during sleep lead to improved performance. From the first we can gain a better understanding of how abnormal dopamine in the forebrain, as in schizophrenics, disrupts working memory and decision-making; from the second we can gain a better understanding of how poor quality sleep can affect learning. Third, with Dr Rasmus Petersen's lab in Manchester, we will analyse their recordings from cells in the centre of the rat's brain that fire in response to movements of their whiskers. Dr Petersen's lab study these cells to understand the basic "neural code", the information that is carried by each spike. They have already found that some cells emit spikes in response to single features of movement, such as the whisker's position or velocity, whereas other cells emit spikes only to a complex mix of these features. We will use my methods to understand how these single cell codes combine when co-ordinated, forming the "population code" for sensory information.

当你思考和行动时，你的大脑发生了什么？细胞发出微小的电脉冲，活动的小尖峰，遍布整个大脑。一些细胞群同时发出这些尖峰，它们都对突然的噪音或你手臂的摆动做出反应。在其他组中，尖峰在细胞中以固定的顺序出现，记住你从前门到公交车站的路径。从根本上说，大脑是通过协调细胞之间的活动来工作的。因此，当细胞停止精确协调时，大脑就会停止正常工作。在癫痫发作时，大脑皮层上的细胞都变得同步，活动的浪潮淹没了肌肉的精细控制。在痴呆症患者中，细胞间同步的丧失阻碍了对过去事件的可靠回忆。我的研究目标是使我们能够发现和分析脑细胞的协调活动。神经科学家现在能够记录数百个独立细胞的峰值，一次持续数小时，来自整个大脑。然而，在没有能力分析这些记录的情况下，由此产生的数据量正在增长。我们有很多方法来比较两个细胞的活性，但很少有方法来比较数百个细胞的活性。在每次记录中，我们找到协调发生的时间的方法甚至更少，或者找出哪些细胞参与了协调，或者找出协调是由同时的尖峰，一个尖峰序列，还是更复杂的东西组成的。如果没有这些方法，这些记录就无法揭示单个细胞的协调活动如何告诉我们大脑的功能和功能障碍。我将开发一种分析方法，能够利用这些记录自动解决所有这些问题：发现细胞何时一起活动，它们属于哪个组，以及协调活动采取何种形式。我将把这些方法应用于神经科学研究的三个领域，它们试图通过同时记录许多细胞来研究健康和疾病中的大脑。首先，我们将与康斯坦斯·哈蒙德博士在马赛的实验室合作，分析他们对大鼠纹状体发育的记录，纹状体是一个巨大的前脑系统，对控制和学习行动都起着核心作用。我们将用我的方法来了解健康纹状体的协调活动在怀孕和婴儿期是如何发展的，然后了解遗传和环境因素是如何破坏这种正确的发展，导致纹状体在青少年时期出现紊乱，比如图雷特综合症。其次，我们将与Sid Wiener博士在巴黎的实验室合作，分析老鼠学习解决迷宫中空间导航任务的前脑记录。我们将用我的方法来了解在学习过程中前脑的协调活动是如何发展的。特别是，我们将分析在正确的任务决策之前突然出现的广泛的协调是如何依赖于多巴胺的，以及在睡眠中重新播放协调活动是如何提高表现的。首先，我们可以更好地了解前脑中的异常多巴胺是如何破坏工作记忆和决策的，就像精神分裂症患者一样；从第二种情况来看，我们可以更好地理解睡眠质量差是如何影响学习的。第三，我们将与曼彻斯特的Rasmus Petersen博士的实验室合作，分析老鼠大脑中心的细胞记录，这些细胞会对胡须的运动做出反应。Petersen博士的实验室通过研究这些细胞来了解基本的“神经密码”，即每个尖峰所携带的信息。他们已经发现，一些细胞对运动的单一特征（如须的位置或速度）会发出尖峰，而另一些细胞只对这些特征的复杂组合发出尖峰。我们将用我的方法来理解这些单细胞密码在协调时是如何结合起来的，形成了感知信息的“种群密码”。