论文标题
单细胞分辨率下癫痫发作的全脑网络动力学
Whole Brain Network Dynamics of Epileptic Seizures at Single Cell Resolution
论文作者
论文摘要
癫痫发作的特征是多个尺度上的脑动力学异常,引人入胜的单神经元,神经元合奏和粗脑区域。理解这种新兴人群动态原因的关键是捕获多个脑尺度上神经元活动的集体行为。在本论文中,我利用幼虫斑马鱼在癫痫发作期间捕获整个大脑中的单细胞神经元活性。首先,我利用统计物理方法来量化癫痫发作期间单个神经元动力学的集体行为。在这里,我演示了一种人群机制,通过该机制,单个神经元动力学将其组织成癫痫发作:脑动力学偏离相变。其次,我利用单个神经元网络模型来识别实际导致这种转变的突触机制。在这里,我表明网络中神经元连接的密度是驱动广义癫痫发作动力学的关键。有趣的是,这种变化还破坏了大脑网络中的网络响应属性和灵活的动态,从而将微观神经元的变化与癫痫发作过程中新兴的脑功能障碍联系起来。第三,我利用非线性因果推理方法来研究能够癫痫发作的潜在神经元相互作用的性质。在这里,我表明癫痫发作是由高同步的驱动,也是由神经元之间高度非线性相互作用驱动的。有趣的是,这些非线性特征在宏观上被过滤,因此可能代表可用于微观介入策略的神经元特征。该论文证明了在幼虫斑马鱼中研究多尺度动力学的实用性,以将微观尺度的神经元活性与癫痫发作期间的新兴特性联系起来。
Epileptic seizures are characterised by abnormal brain dynamics at multiple scales, engaging single neurons, neuronal ensembles and coarse brain regions. Key to understanding the cause of such emergent population dynamics, is capturing the collective behaviour of neuronal activity at multiple brain scales. In this thesis I make use of the larval zebrafish to capture single cell neuronal activity across the whole brain during epileptic seizures. Firstly, I make use of statistical physics methods to quantify the collective behaviour of single neuron dynamics during epileptic seizures. Here, I demonstrate a population mechanism through which single neuron dynamics organise into seizures: brain dynamics deviate from a phase transition. Secondly, I make use of single neuron network models to identify the synaptic mechanisms that actually cause this shift to occur. Here, I show that the density of neuronal connections in the network is key for driving generalised seizure dynamics. Interestingly, such changes also disrupt network response properties and flexible dynamics in brain networks, thus linking microscale neuronal changes with emergent brain dysfunction during seizures. Thirdly, I make use of non-linear causal inference methods to study the nature of the underlying neuronal interactions that enable seizures to occur. Here I show that seizures are driven by high synchrony but also by highly non-linear interactions between neurons. Interestingly, these non-linear signatures are filtered out at the macroscale, and therefore may represent a neuronal signature that could be used for microscale interventional strategies. This thesis demonstrates the utility of studying multi-scale dynamics in the larval zebrafish, to link neuronal activity at the microscale with emergent properties during seizures.