NEUROTROPHIN ACTIONS ON V PRIMARY AFFERENT DEVELOPMENT

拟议中的研究将检验与胡须相关的一般假设 模式的形成是神经营养调节的直接结果， 三叉神经节内自然发生的细胞死亡。解剖学 电生理方法将与各种 胎儿神经营养素强化方案确定其作用机制 神经营养素诱导的V型原发灶失败的原因 传入神经元。三个具体目标是； 1)作为表征神经营养因子-4/5-NNT-作用的第一步 4/5在V系统的开发中，V主要传入投影将 在胎鼠补充NT-4/5水平后进行研究。 2)确定神经生长因子(NGF)和NT-4/5是否对 胎儿神经节细胞选择性群体的存活，这两个 神经促性腺激素将在胎鼠身上得到增强。以不同的间隔，V 将对神经节进行免疫组织化学处理，以寻找特定的标志物 神经节细胞的类型。 3)评价NGF和NT-4/5对中枢V波的作用 是由于外周投射改变(神经营养效应)， 胡须垫的神经支配将在神经营养学中进行研究 使用轴突内标记，逆行双重标记， 信号单位记录、电子显微镜和免疫组织化学轴突 染色方法。 这些实验在本计划项目中进行得最有效 由于提供的专业知识、基准数据和材料， DRS/安德拉德，贝内特-克拉克，戈尔登，雅克，约翰逊，罗瓦兹，赖斯， 伍尔西和扎姆。核心的“形态测量”和“EM”设施也将被使用 广泛地。神经营养素和化验将由E.M.约翰逊博士提供 还有Regeneron。 拟议的实验可能会牵涉到帮助躯体感觉的一般原则 人类的发展，因为最近的迹象表明，人类 胞核内的体细胞分裂、桶状聚集 主核和背柱核(Noriega和Wall‘91)。 此外，神经营养因子的生物学作用将揭示可能 在治疗某些神经性疾病方面有未来的用处

Proposed studies will test the general hypothesis that whisker-related pattern formation occurs as a direct result of neurotrophically regulated, naturally occurring cell death in the t rigeminal (V) ganglion. Anatomical and electrophysiological methods will be used in conjunction with various fetal neurotrophin augmentation regimens to determine mechanisms responsible for neurotrophin-induced failed pattern formation in V primary afferent neurons. Three Specific Aims are; 1) As the initial step in characterizing the role of neurotrophin-4/5 NNT- 4/5 in the development of the V system, V primary afferent projections will be studied after supplementating NT-4/5 levels in fetal rats. 2) To determine whether nerve growth factor (NGF) and NT-4/5 impact on the survival of selective populations of fetal ganglion cells, these two neurotropins will be augmented in fetal rats. At varying intervals, V ganglia will be processed immunohistochemically for markers of specific types of gangglion cells. 3) To assess whether the actions of NGF and NT-4/5 on central V patterns are due to altered peripheral projections (neurotropic effects), the innervation of the whiskerpad will be studied in neurotrophically manipulated arats using intra-axonal labeling, retrograde double-labeling, signle unit recording, electron microscopic, and immunohistochemical axon staining methods. These experiments are most efficiently carried out in this Program Project because of the expertise, baseline data, and materials made available by Drs/ Andrade, Bennett-Clarke, Golden, Jacquin, Johnson, Rhooades, Rice, Woolsey and Zahm. CORE "morphometry" and "EM" facilities will also be used extensively. Neurotrophins and assays will be provided by Dr. E.M. Johnson and Regeneron. Proposed experiments may implicate general principles suiding somatosensory development in humans because of recent indications that humans have somatotopically parcellated, barrel-like aggregations in nucleus principalis and the dorsal column nuclei (Noriega and Wall '91). In addition, biological actions of neurotrophic factors will revealed that may be of future use in treating certain neuropathic disorders