Pruning of Motor Neuronal Arbors

运动神经元乔木的修剪

• 批准号: 6596902
• 负责人: JOYCE J FERNANDES
• 金额: $ 21万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6596902
• 关键词: Drosophilidae; arthropod genetics; biological models; developmental genetics; developmental neurobiology; electrophysiology; metamorphosis; motor neurons; mutant; neural plasticity; neurogenesis; neuromuscular junction; neuronal transport; synaptogenesis

DESCRIPTION (provided by applicant): The long-term goal of this research is to understand the cellular and molecular mechanisms of cell-cell communication between a motor neuron and muscle fiber during the formation of a functional synapse. Specifically, we want to address how motor neurons are remodeled during the development of an adult nervous system. We use the (adult) Dorsal Longitudinal (flight) Muscle synapse of Drosophila as a model. We previously showed that the basic neuromuscular pattern of the DLMs develops during the first day of metamorphosis, and described the remodeling of persistent larval motor neurons to innervate adult muscle targets. This proposal focuses on the remaining 3 days of the pupal phase, and examines how adult-specific motor neuronal arbors are pruned back and stabilized to give rise to the mature adult DLM synapse. The synaptic plasticity evident during this process is more pronounced than changes such as those occurring during larval synaptic growth, and bears striking similarities to synapse refinement seen in vertebrate nervous systems. We hope to demonstrate that the (adult) DLM synapse has many characteristics of its vertebrate counterpart. Three main objectives are presented: a) Identify the precise time period during which pruning of peripheral motor neuronal arbors occurs. b) Use genetic and electrophysiological approaches to examine the role of electrical activity in pruning. c) Follow the maturation of neuromuscular contacts into functional synapses using synapse-specific markers and ultrastructural approaches. Most of the studies on synapse formation and maturation in Drosophila have focused on the embryonic and the larval system while development of the adult synapse remains to be explored in the same detail. Since persistent larval motor neurons are respecified to become adult motor neurons, our studies of pruning during metamorphosis will describe an additional level of synaptic plasticity of these motor neurons that occurs during the adult (second) phase of synaptogenesis. Embryonic and adult NMJ formation have previously been studied in isolation. Our studies will serve to strengthen the continuity between the two remarkably distinct stages in the Drosophila life cycle, and serve as a basis for further studies on understanding the molecular bases of the differences and similarities with respect to synaptogenesis. In doing so, we hope to better understand the nature of cell-communication between pre- and post-synaptic cells (retrograde and anterograde signaling) that is central to the manifestation of synaptic plasticity. These studies will have implications for better understanding the neurodevelopmental basis of diseases such as epilepsy, schizophrenia and Rett's syndrome, where pruning is thought to be defective.

描述(申请人提供)：这项研究的长期目标是了解在功能性突触形成过程中运动神经元和肌肉纤维之间细胞-细胞通讯的细胞和分子机制。具体地说，我们想要解决运动神经元在成人神经系统发育过程中是如何重塑的。我们以果蝇的(成体)背纵(飞)肌突触为模型。我们以前证明了DLMS的基本神经肌肉模式是在变态的第一天发展起来的，并描述了持续性幼虫运动神经元的重塑来支配成年肌肉靶点。这项建议侧重于蛹阶段的剩余3天，并研究了成虫特有的运动神经元茎是如何被修剪和稳定以产生成熟的成年DLm突触的。在这个过程中，突触的可塑性比幼虫突触生长过程中发生的变化更明显，与脊椎动物神经系统中的突触细化有惊人的相似之处。我们希望证明(成年)DLm突触具有脊椎动物突触的许多特征。提出了三个主要目标：a)确定发生外周运动神经元束修剪的准确时间段。B)使用遗传和电生理方法研究电活动在修剪中的作用。C)使用突触特异性标记物和超微结构方法跟踪神经肌肉接触成熟为功能性突触的过程。关于果蝇突触的形成和成熟的研究大多集中在胚胎和幼虫系统，而成体突触的发育还有待于详细的探讨。由于持久性幼虫运动神经元被重新指定为成年运动神经元，我们对变态期间修剪的研究将描述这些运动神经元在成体(第二)突触发生阶段发生的额外水平的突触可塑性。胚胎和成体的NMJ形成之前已经被孤立地研究过。我们的研究将有助于加强果蝇生活史上两个截然不同的阶段之间的连续性，并为进一步研究突触发生方面的差异和相似之处的分子基础奠定基础。通过这样做，我们希望更好地了解突触前和突触后细胞之间的细胞交流的本质(逆行和顺行信号)，这是突触可塑性表现的核心。这些研究将有助于更好地理解癫痫、精神分裂症和雷特氏综合症等疾病的神经发育基础，这些疾病的修剪被认为是有缺陷的。