AXOPLASMIC TRANSPORT AND CENTRAL TRIGEMINAL PATTERN MAINTENANCE

轴浆运输和中央三叉神经模式维持

• 批准号: 6451071
• 负责人: NICOLAS Louis CHIAIA
• 金额: $ 8.74万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6451071
• 关键词: afferent nerve; brain regulatory center; developmental neurobiology; genetically modified animals; laboratory mouse; laboratory rat; neuronal transport; neurotrophic factors; spinal trigeminal nucleus; trigeminal nerve; vibrissae; vinblastine

Ordered representations of the craniofacial periphery in the brain are necessary for normal sensory and motor functions of the face and head. While considerable experimental attention has been paid to the development and plasticity of central nervous system craniofacial representations, we still do not understand how they are maintained throughout life. The overall aim of the proposed research is to understand the necessary conditions for maintenance of peripherally determined central patterns of neuronal cell bodies and processes in the rodent trigeminal (V) system. We recently showed that attenuation of axonal transport in the infraorbital nerve (ION) with vinblastine results in a loss of all central fibrissae-related patterns. This is the only postnatal manipulation other than ION transection that has ever been demonstrated to have this effect and it occurs even though V primary afferent neurons in vinblastine-treated nerve maintain qualitatively normal projections to the periphery and brainstem. Our working hypothesis is that two conditions are necessary for the preservation of vibrissae-related patterns in the V brainstem complex: arrangement of the central arbors of vibrissae-related V ganglion cells in a pattern corresponding to the vibrissae; and, delivery of a peripherally derived neurotrophic factor by these primary afferents to V brainstem neurons In this "model," the vibrissae-related patterning of central ION axons provides correspondingly patterned concentrations gradients of the trophic factor which, in turn, result in the maintained aggregation of brainstem neurons. The patterning of cells in V nucleus principalis is required for the development and maintenance of corresponding vibrissae-related patterns in thalamus and cortex. While any of several neurotrophins might support the maintenance of central V patterns following transection of, or application of vinblastine to, the developing ION: 1) These manipulations cause a loss of central patterns secondary to the death of V ganglion and brainstem cells. 2) Central pattern loss results from lesion-induced abnormal functional input to the developing brainstem cells. 2) Central pattern loss results from lesion-induced abnormal functional input to the developing V brainstem complex. 3) The dramatic up-regulation of specific peptides (galanin and neuropeptide Y0 in input to the developing brainstem complex. Y) in surviving V ganglion cells and their central axons contribute to the loss of central vibrissae-related patterns after attenuation of axoplasmic transport or damage to, the ION. The experiments in this application will test our working hypothesis as well as these other possibilities regarding the mechanisms underlying the loss of central V patterns after application of vinblastine to the ION in newborn rats.

大脑中颅面周边的有序表征对于面部和头部的正常感觉和运动功能是必要的。虽然相当多的实验注意力已经支付给中枢神经系统颅面表征的发展和可塑性，我们仍然不知道他们是如何维持整个生命。拟议的研究的总体目标是了解维持啮齿动物三叉神经（V）系统中神经元细胞体和过程的外周决定的中枢模式的必要条件。我们最近发现，长春碱导致眶下神经（ION）轴突运输的衰减导致所有中枢纤维相关模式的丧失。这是唯一的出生后操作以外的离子横断，已被证明有这种效果，即使在长春碱处理的神经V初级传入神经元保持定性正常的投射到外周和脑干。我们的工作假设是，在V脑干复合体中保存触须相关的模式需要两个条件：触须相关的V神经节细胞的中央分支以与触须对应的模式排列;以及通过这些初级传入神经将外周来源的神经营养因子递送至V脑干神经元在该“模型”中，中央ION轴突的触须相关图案提供了相应图案化的营养因子浓度梯度，这反过来导致脑干神经元的持续聚集。V主核中细胞的图案化是丘脑和皮质中相应触须相关图案的发展和维持所必需的。虽然几种神经营养因子中的任何一种都可能支持在切断或应用长春碱后维持中枢V模式，但发展中的ION：1）这些操作导致继发于V神经节和脑干细胞死亡的中枢模式丧失。2)中枢型丢失是由损伤诱导的发育中的脑干细胞的异常功能输入引起的。2)中枢型丢失是由于损伤诱导的异常功能输入到发育中的V脑干复合体所致。3)特定肽（甘丙肽和神经肽Y 0）在发育中的脑干复合体输入中的显著上调。Y）在存活的V神经节细胞和它们的中央轴突中的表达有助于在轴浆运输减弱或对ION的损伤后中央触须相关模式的丧失。本申请中的实验将检验我们的工作假设以及关于在新生大鼠中将长春碱应用于ION后中央V模式丢失的潜在机制的这些其他可能性。