Axonal arborization of sensory neurons in zebrafish

斑马鱼感觉神经元的轴突树枝化

• 批准号: 7569425
• 负责人: YUCHIN Albert Pan
• 金额: $ 5.17万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7569425
• 关键词: Acute; Address; Adopted; Afferent Neurons; Animals; Area; Axon; Biological Models; Brain region; Cells; Chronic; Detection; Development; Head; Imagery; Individual; Label; Life; Neurons; Nociception; Pain; Patients; Pattern; Peripheral; Proteins; Role; Sense Organs; Sensory Ganglia; Signal Transduction; Skin; Source; Stimulus; Synapses; Trigeminal System; Zebrafish; density; neurotrophic factor; receptor; relating to nervous system; sensory stimulus; therapy development

DESCRIPTION (provided by applicant): Pain, either acute or chronic, is a source of everyday agony for millions of patients. Understanding the components of nociception--the detection of harmful stimuli by sensory neurons-would greatly facilitate development of treatments for pain. In this proposal, I will investigate the development of the trigeminal sensory ganglia, the major organ for sensing potentially harmful (noxious) stimuli to the head. During development, a trigeminal sensory neuron (TGN) extends two types of projections: a peripheral axon and a central axon. The peripheral axon innervates the skin of the head and receives sensory stimuli; the central axon, in contrast, projects to deep brain regions and synapses on to neurons. The correct pattern of axonal arborization is crucial forTGN's function, but the mechanism by which this is achieved is unclear. To address these questions, I adopted the zebrafish TGN as a model system because it allows direct visualization and manipulation of growing axonal arbors in live, behaving animals at the single cell level. Specific Aim 1: The roles of neural activity in peripheral axonal arborization. To investigate the roles of neural activity in peripheral axon arborization, I will inactivate individual TGNs and determine their arborization pattern with respect to their neighbors. Specific Aim 2: The role of neurotrophins in peripheral axonal arborization. To investigate the role of neurotrophin signaling on the size and density of the peripheral axonal arbors, I will block or activate Trk receptors and determine the arborization pattern of TGNs. Specific Aim 3: Central axon projection of TGN neurons. To determine the central projection pattern of TGNs, I will use photoconvertible and photoactivatable fluorescent proteins to label central axons of individual neurons and determine whether there is topographic projection that corresponds to the receptive area in the head. Relevance: Understanding the components of nociception would greatly facilitate development of treatments for pain. I propose to investigate the development of the trigeminal sensory ganglia, the major organ for sensing noxious stimuli to the head.

描述（由申请人提供）：急性或慢性疼痛是数百万患者的日常痛苦来源。了解伤害感受的成分 - 感觉神经元对有害刺激的检测，将大大促进疼痛治疗的发展。在此提案中，我将研究三叉神经节的发展，这是将潜在有害（有害的）刺激感传感到头部的主要器官。在开发过程中，三叉神经元（TGN）扩展了两种类型的投影：外围轴突和中央轴突。外围轴突支配头部的皮肤并接收感觉刺激；相比之下，中央轴突将深脑区域和突触投影到神经元上。正确的轴突树木化模式是至关重要的Fortgn功能，但是实现这一目标的机制尚不清楚。为了解决这些问题，我采用了斑马鱼TGN作为模型系统，因为它可以直接可视化和操纵现场生长的轴突轴，并在单细胞水平上表现动物。特定目标1：神经活动在外周轴突植物化中的作用。为了研究神经活性在外周轴突树博化中的作用，我将使单个TGN失活并确定其相对于其邻居的树博模式。特定目标2：神经营养蛋白在周围轴突一半上的作用。为了研究神经营养蛋白信号传导对周围轴突轴的大小和密度的作用，我将阻止或激活TRK受体并确定TGN的树博模式。特定目标3：TGN神经元的中央轴突投影。为了确定TGN的中心投影模式，我将使用光旋转和光活化荧光蛋白来标记单个神经元的中央轴突，并确定是否有与头部接受区域相对应的地形投影。相关性：了解伤害感受的成分将极大地促进疼痛治疗的发展。我建议研究三叉神经节的发展，这是向头部传感有害刺激的主要器官。