NEUROTROPHIN ACTIONS ON V PRIMARY AFFERENT DEVELOPMENT

拟议中的研究将检验与胡须有关的一般假设， 模式形成是神经营养调节的直接结果， 三叉神经（V）神经节中自然发生的细胞死亡。 解剖 电生理学方法将与各种 胎儿神经营养素增强方案，以确定机制 负责神经营养因子诱导的V型原发性 传入神经元 三个具体目标是： 1)作为表征神经营养素-4/5 NNT作用的第一步， 4/5在V系统的发育中，V初级传入投射将 测定胎鼠NT-4/5水平。 2)为了确定神经生长因子（NGF）和NT-4/5是否影响 胎儿神经节细胞的选择性群体的存活，这两个 神经营养素将在胎鼠中增加。 在不同的时间间隔，V 神经节将被化学处理，用于特异性 神经节细胞的类型。 3)评估NGF和NT-4/5对中枢V型的作用是否与其对中枢V型的影响有关。 是由于外周投射改变（亲神经效应）， 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，逆行双标记， 单单位记录、电镜和免疫组织化学轴突 染色方法 这些实验在本项目中进行得最为有效 由于专业知识，基线数据和材料， Andrade、Bennett-Clarke、Golden、Jacquin、约翰逊、Rhooades、Rice博士， 伍尔西和扎姆 还将使用CORE的“形态测定”和“EM”设施 广泛地。 神经营养素和测定将由EM博士提供约翰逊 还有Regeneron 拟议的实验可能涉及的一般原则， 由于最近的迹象表明，人类有 核内体细胞定位包裹的桶状聚集体 principalis和背柱核（Noriega和Wall '91）。 在 此外，还将揭示神经营养因子的生物学作用， 在未来用于治疗某些神经病性疾病

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