Developmental roles of spontaneous network activity during motor circuit assembly

运动电路组装过程中自发网络活动的发展作用

• 批准号: BB/F01516X/1
• 负责人: Jonathan McDearmid
• 金额: $ 39.49万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF01516X%2F1
• 关键词: Developmental; roles; spontaneous; network; activity

Cells of the adult brain are organised into a vast array of networks that relay, process and respond to information from the external world. These networks are composed of neurons, specialized cells that carry electrical information. Neurons within networks communicate with one another by releasing neurotransmitters, small chemical messengers, across specialized junctions called synapses. By using a combination of electrical and chemical signalling, neuronal networks of the adult brain can process and respond to a wide spectrum of information from the environment. Until recently, it was believed that the embryonic brain does not generate activity before sensory systems develop. However, recent research has demonstrated that this is not the case. Immature neuronal networks spontaneously generate patterns of electrical activity in the absence of sensory input. This activity is unique to developing networks, bearing no resemblance to activities seen in the adult brain. Such spontaneous activity is observed in the brains of virtually all developing animals. Whilst it is known to be important for maturation of nervous tissue, its role during early development remains poorly described. We will address this problem by studying network activity during development of the zebrafish embryo. The zebrafish, a small freshwater cyprinid, is ideal for developmental studies because fertilization occurs externally so that steps during embryonic development can be easily monitored. In the zebrafish embryo, before sensory systems are established, immature neuronal networks generate spontaneous activity. It is our goal to establish precisely how such activity is generated and how it influences the early stages of development. Our work has two broad goals. The first is to understand how the immature network produces activity. To do this we will monitor electrical properties of developing embryonic neurons. We will examine how these neurons are able to spontaneously generate electrical activity in the absence of external input. Our second goal will be to determine developmental roles of early activity in the zebrafish embryo. We will use molecular genetic methods to disrupt electrical signals and determine how this influences network maturation. We will focus on the neuronal network that generates swimming as it can be used as a simple model network for the study of behaviour. In this way we will be able to examine how early network activity affects many aspects of development, from the growth of individual neurons through to the maturation of adult behaviours. Our work will cast new light on the importance of electrical activity in the embryonic nervous system and may provide important clues about how aberrant activity causes developmental disease.

成年人的大脑细胞被组织成一个庞大的网络，这些网络中继，处理和响应来自外部世界的信息。这些网络由神经元组成，神经元是携带电信息的专门细胞。网络中的神经元通过释放神经递质（一种小的化学信使）穿过称为突触的专门连接点进行相互交流。通过使用电和化学信号的组合，成年人大脑的神经元网络可以处理和响应来自环境的广泛信息。直到最近，人们才相信胚胎大脑在感觉系统发育之前不会产生活动。然而，最近的研究表明，情况并非如此。不成熟的神经元网络在没有感觉输入的情况下自发地产生电活动模式。这种活动是发育中的网络所特有的，与成人大脑中的活动没有任何相似之处。这种自发活动在几乎所有发育中的动物的大脑中都可以观察到。虽然已知它对神经组织的成熟很重要，但其在早期发育过程中的作用仍然很少描述。我们将通过研究斑马鱼胚胎发育过程中的网络活动来解决这个问题。斑马鱼是一种小型淡水鲤科鱼类，是发育研究的理想选择，因为受精发生在外部，因此可以很容易地监测胚胎发育过程中的步骤。在斑马鱼胚胎中，在感觉系统建立之前，未成熟的神经元网络产生自发活动。我们的目标是准确地确定这种活动是如何产生的，以及它如何影响发展的早期阶段。我们的工作有两大目标。第一个是了解不成熟的网络如何产生活动。为此，我们将监测发育中的胚胎神经元的电特性。我们将研究这些神经元如何能够在没有外部输入的情况下自发地产生电活动。我们的第二个目标是确定斑马鱼胚胎早期活动的发育作用。我们将使用分子遗传学方法来破坏电信号，并确定这如何影响网络成熟。我们将专注于产生游泳的神经元网络，因为它可以用作行为研究的简单模型网络。通过这种方式，我们将能够研究早期网络活动如何影响发育的许多方面，从单个神经元的生长到成人行为的成熟。我们的工作将为电活动在胚胎神经系统中的重要性提供新的线索，并可能为异常活动如何导致发育疾病提供重要线索。

项目成果

Pacemaker and plateau potentials shape output of a developing locomotor network.

• DOI: 10.1016/j.cub.2012.10.025
• 发表时间: 2012-12-18
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Tong, Huaxia;McDearmid, Jonathan Robert
• 通讯作者: McDearmid, Jonathan Robert

Early interneuron dysfunction in ALS: insights from a mutant sod1 zebrafish model.

• DOI: 10.1002/ana.23780
• 发表时间: 2013-02
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: McGown, Alexander;McDearmid, Jonathan R.;Panagiotaki, Niki;Tong, Huaxia;Al Mashhadi, Sufana;Redhead, Natasha;Lyon, Alison N.;Beattie, Christine E.;Shaw, Pamela J.;Ramesh, Tennore M.
• 通讯作者: Ramesh, Tennore M.