Networks of neural dynamics: Knowledge-discovery for experimental neuroscience

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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.