Axonal arborization of sensory neurons in zebrafish

斑马鱼感觉神经元的轴突树枝化

• 批准号: 7351818
• 负责人: YUCHIN Albert Pan
• 金额: $ 4.96万
• 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/7351818
• 关键词: Acute; Address; Adopted; Afferent Neurons; Animals; Area; Axon; Biological Models; Brain region; Cells; Chromosome Pairing; Chronic; Depth; 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; size; 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）：疼痛，无论是急性还是慢性，都是数百万患者日常痛苦的根源。了解伤害感受的组成部分——感觉神经元对有害刺激的检测——将极大地促进疼痛治疗的发展。在本提案中，我将研究三叉神经感觉神经节的发育，三叉神经感觉神经节是感知对头部潜在有害（有害）刺激的主要器官。在发育过程中，三叉神经感觉神经元（TGN）延伸出两种类型的投射：外周轴突和中央轴突。外周轴突支配头部皮肤并接收感觉刺激；相比之下，中央轴突投射到大脑深处区域，并将突触投射到神经元上。轴突树枝化的正确模式对于 TGN 的功能至关重要，但实现这一点的机制尚不清楚。为了解决这些问题，我采用斑马鱼 TGN 作为模型系统，因为它允许在单细胞水平上直接可视化和操作活体、行为动物中生长的轴突乔木。具体目标 1：神经活动在外周轴突树枝化中的作用。为了研究神经活动在外周轴突树枝化中的作用，我将灭活单个 TGN 并确定它们相对于邻居的树枝化模式。具体目标 2：神经营养素在外周轴突树枝化中的作用。为了研究神经营养蛋白信号传导对外周轴突乔木大小和密度的作用，我将阻断或激活 Trk 受体并确定 TGN 的乔木化模式。具体目标 3：TGN 神经元的中央轴突投射。为了确定 TGN 的中心投影模式，我将使用光转换和光激活荧光蛋白来标记单个神经元的中心轴突，并确定是否存在与头部接收区域相对应的地形投影。相关性：了解伤害感受的组成部分将极大地促进疼痛治疗方法的开发。我建议研究三叉神经感觉神经节的发育，三叉神经感觉神经节是感知头部有害刺激的主要器官。