Our understanding of the genetic aetiology of paediatric epilepsies has grown substantially over the last decade. However, in order to translate improved diagnostics to personalised treatments, there is an urgent need to link molecular pathophysiology in epilepsy to whole-brain dynamics in seizures. Zebrafish have emerged as a promising new animal model for epileptic seizure disorders, with particular relevance for genetic and developmental epilepsies. As a novel model organism for epilepsy research they combine key advantages: the small size of larval zebrafish allows high throughput in vivo experiments; the availability of advanced genetic tools allows targeted modification to model specific human genetic disorders (including genetic epilepsies) in a vertebrate system; and optical access to the entire central nervous system has provided the basis for advanced microscopy technologies to image structure and function in the intact larval zebrafish brain. There is a growing body of literature describing and characterising features of epileptic seizures and epilepsy in larval zebrafish. Recently genetically encoded calcium indicators have been used to investigate the neurobiological basis of these seizures with light microscopy. This approach offers a unique window into the multiscale dynamics of epileptic seizures, capturing both whole-brain dynamics and single-cell behaviour concurrently. At the same time, linking observations made using calcium imaging in the larval zebrafish brain back to an understanding of epileptic seizures largely derived from cortical electrophysiological recordings in human patients and mammalian animal models is non-trivial. In this review we briefly illustrate the state of the art of epilepsy research in zebrafish with particular focus on calcium imaging of epileptic seizures in the larval zebrafish. We illustrate the utility of a dynamic systems perspective on the epileptic brain for providing a principled approach to linking observations across species and identifying those features of brain dynamics that are most relevant to epilepsy. In the following section we survey the literature for imaging features associated with epilepsy and epileptic seizures and link these to observations made from humans and other more traditional animal models. We conclude by identifying the key challenges still facing epilepsy research in the larval zebrafish and indicate strategies for future research to address these and integrate more directly with the themes and questions that emerge from investigating epilepsy in other model systems and human patients.

中文翻译：

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斑马鱼幼虫癫痫的成像

在过去的十年里，我们对小儿癫痫遗传病因学的了解有了很大的发展。然而，为了将改进的诊断转化为个性化治疗，迫切需要将癫痫的分子病理生理学与癫痫发作的全脑动力学联系起来。斑马鱼已成为治疗癫痫发作疾病的一种有前途的新动物模型，特别是与遗传性和发育性癫痫相关。作为癫痫研究的新型模型生物，它们结合了关键优势：斑马鱼幼体体积小，可以进行高通量的体内实验；先进的遗传工具的可用性允许有针对性的修改来模拟脊椎动物系统中特定的人类遗传疾病（包括遗传性癫痫）；对整个中枢神经系统的光学访问为先进显微镜技术提供了基础，以对完整幼虫斑马鱼大脑的结构和功能进行成像。越来越多的文献描述和描述了斑马鱼幼虫癫痫发作和癫痫的特征。最近，基因编码的钙指示剂已被用于通过光学显微镜研究这些癫痫发作的神经生物学基础。这种方法为了解癫痫发作的多尺度动力学提供了一个独特的窗口，同时捕获全脑动力学和单细胞行为。与此同时，将幼虫斑马鱼大脑中钙成像的观察结果与对癫痫发作的理解联系起来并非易事，癫痫发作主要来源于人类患者和哺乳动物模型的皮层电生理记录。在这篇综述中，我们简要介绍了斑马鱼癫痫研究的最新技术，特别关注幼虫斑马鱼癫痫发作的钙成像。我们说明了癫痫大脑动态系统视角的实用性，它提供了一种原则性方法来连接跨物种的观察结果并识别与癫痫最相关的大脑动力学特征。在下一节中，我们调查了与癫痫和癫痫发作相关的影像学特征的文献，并将这些与人类和其他更传统的动物模型的观察结果联系起来。最后，我们确定了斑马鱼幼虫癫痫研究仍然面临的关键挑战，并指出了未来研究的策略，以解决这些问题，并更直接地与其他模型系统和人类患者癫痫研究中出现的主题和问题结合起来。