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(申请人提供)：疼痛，无论是急性的还是慢性的，都是数百万患者日常痛苦的来源。了解伤害感的组成部分--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。在这项建议中，我将研究三叉神经节的发育，三叉神经感觉神经节是感知头部潜在有害(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，接受感官刺激；相反，中央轴突投射到大脑深层区域，并与神经元突触。正确的轴突分支模式对TGN的功能至关重要，但实现这一功能的机制尚不清楚。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纵活的、行为正常的动物的轴突乔木生长。具体目标1：神经活动在外周轴突分支中的作用。为了研究神经活动在外周轴突树枝形成中的作用，我将灭活单个中缝大核，并确定它们相对于相邻神经元的树枝模式。具体目标2：神经营养因子在外周轴突分支中的作用。为了研究神经营养因子信号在外周轴索的大小和密度中的作用，我将阻断或激活Trk受体，并确定TGNs的树枝模式。具体目标3：TGN神经元的中枢轴突投射。为了确定TGNs的中心投影模式，我将使用光转换和光激活的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感受区相对应的地形图投影。相关性：了解伤害感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感觉神经节的发育，三叉神经感觉神经节是感知头部伤害性刺激的主要器官。