MECHANISMS OF DAMAGE-INDUCED TRIGEMINAL REORGANIZATION

损伤引起的三叉神经重组机制

基本信息

批准号：
6710167
负责人：
MARK F JACQUIN
金额：
$ 79.62万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-12-01 至 2005-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6710167
关键词：
central neural pathway /tract developmental neurobiology neurogenesis neurotrophic factors trigeminal nerve

项目摘要

Ongoing collaborations between neuroscientists at the Washington University School of Medicine, Medical College of Ohio, University of Kansas, and Louisiana State University will continue to address mechanisms responsible for normal development and injury-induced reorganization in mammalian sensory systems. The central trigeminal (V) representation of the rodent whiskers (barrels) and limbs will be used to test hypotheses pertaining to: 1) neutrophic regulation of sensory axon growth rate and mode during development; 2) neurotrophin-regulated axon branching and sensory end-organ morphogenesis; 3) mechanism underlying the loss of central V barrel-like patterns after interruption of axonal transport in the developing V nerve; 4) neutrophic control of thalamocortical development; 5) the role of a serotonin receptor and transporter in barrel development and thalamocortical axon outgrowth; and 6) mechanisms subserving cortical expression of sensory information after neonatal limb amputation. An Administrative/Morphology CORE (A) will provide a single neuron labeling facility, electron microscopy, administrative support, and ensure timely communication between projects and external review. A Transgenic Mouse CORE (B) will generate new transgenic models where neurotrophin expression is induced and regulated in selected targets during specified periods in development. An Image Analysis and Morphometry CORE (C) offers a variety of standardized options for quantitative analyses of relevant features in histological preparations. PROJECT 1 will use in vitro organotypic tissue culture and in vivo transgenic over-expression methods to uncover neurotrophin actions during developing V primary afferents and whisker-related pattern formation. PROJECT 2 will assess how the neurotrophin NT3, and the transcription factor, Egr3, regulate the development of limb proprioceptive axons and how these actions modify the function of muscle spindles. PROJECT 3 will reveal the necessary conditions for maintenance of patterns in the V neuraxis; anatomical methods will test the hypothesis that attenuation of axoplasmic transport in the immature V nerve causes a disappearance of central barrel-like patterns secondary to the loss of patterned delivery in neurotrophin from the periphery to the brainstem. PROJECT 4 will use mice with augmented levels of cortical neurotrophins produced by controlled transgenic over-expression in host or transplanted embryonic stem cells, to test the hypothesis that development, and that the spatial and temporal distribution of neurotrophins determines thalamocortical structure and function. PROJECT 4 will employ transgenic mice and pharmacologic methods to test the hypothesis that the 5THT1B receptor and the serotonin transporter mediate the activity-independent effects of serotonin on thalamocortical development. PROJECT 6 uses anatomic, pharmacologic, and electrophysiologic methods to reveal substrates for altered sensory information processing in the S1 cortex after neonatal forelimb removal.

华盛顿大学医学院，俄亥俄州医学院，堪萨斯大学和路易斯安那州立大学的神经科学家之间的持续合作将继续解决负责正常发展的机制，并在哺乳动物感觉系统中进行正常发展和受伤引起的重组。啮齿动物（桶）和四肢的中央三叉神经（V）表示，用于检验有关：1）在发育过程中感觉轴突生长速率和模式的中性粒子调节； 2）神经营养蛋白调节的轴突分支和感觉最终器官形态发生； 3）在发育中的V神经中中断轴突转运后，中央V型枪管样模式损失的基础机制； 4）丘脑皮质发育的中性细胞控制； 5）5-羟色胺受体和转运蛋白在枪管发育和丘脑皮质轴突生长中的作用； 6）新生儿肢体截肢后感觉信息的皮质表达的机制。行政/形态核心（A）将提供单个神经元标签设施，电子显微镜，管理支持，并确保项目和外部审查之间及时沟通。转基因小鼠核（B）将生成新的转基因模型，在该模型中，在开发的指定期间，在所选靶标中诱导神经营养蛋白表达并调节。图像分析和形态计量学核心（C）提供了各种标准化选项，用于定量分析组织学制剂中相关特征。项目1将使用体外器官组织培养和体内转基因过表达方法在开发V主要传入和晶须相关的模式形成过程中发现神经营养蛋白的作用。项目2将评估神经营养蛋白NT3和转录因子EGR3如何调节肢体前感受轴突的发展以及这些动作如何修饰肌肉纺锤体的功能。项目3将揭示维神经模式维持的必要条件；解剖学方法将检验以下假设：未成熟神经中轴质转运的衰减会导致中央桶状模式消失，这是从周围向周围递送到脑干中神经营养蛋白中图案化递送的损失。项目4将使用与受控转基因过表达在宿主或移植的胚胎干细胞中产生的增强水平的皮质神经营养蛋白的小鼠，以测试发育的假说，以及神经营养蛋白的空间和时间分布决定了丘脑皮质的结构和功能。项目4将采用转基因小鼠和药理学方法来检验以下假设：5THT1B受体和5-羟色胺转运蛋白介导5-羟色胺对丘脑皮质发育的活性非依赖性作用。项目6使用解剖，药理和电生理方法来揭示新生儿前肢去除后S1皮质中改变感觉信息处理的底物。