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: 6584616
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584616
• 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.

面部和头部的正常感觉和运动功能需要大脑中颅面外周的有序表征。虽然对中枢神经系统颅面表征的发育和可塑性已经给予了相当大的实验关注，但我们仍然不清楚它们是如何在一生中保持的。这项拟议研究的总体目标是了解啮齿动物三叉神经(V)系统中维持外周决定的神经元胞体和突起的中枢模式的必要条件。我们最近发现，用长春花碱减弱眶下神经(ION)的轴突运输会导致所有中枢纤维相关模式的丧失。这是除离子切断外唯一被证明具有这种作用的出生后手法，即使长春花碱治疗的神经中的V初级传入神经元维持着定性正常的外周和脑干投射也会发生。我们的工作假设是，在V脑干复合体中保存触觉相关模式需要两个条件：与触须相关的V神经节细胞的中心茎以与触须相对应的模式排列；以及通过这些初级传入向V脑干神经元输送外周派生的神经营养因子。在这个“模型”中，中央离子轴突的触须相关模式提供了相应的营养因子浓度梯度，这反过来又导致脑干神经元的维持聚集。V主核中细胞的图案化是丘脑和皮质中相应的触觉相关模式的发展和维持所必需的。在切断或应用长春花碱后，任何一种神经营养因子都可能支持中枢V型模式的维持：1)这些操作导致继发于V型神经节和脑干细胞死亡的中枢模式的丧失。2)中枢模式的丧失是由于病变导致发育中的脑干细胞的异常功能输入。2)中枢模式的丧失是由于病变引起的对发育中的V脑干复合体的异常功能输入所致。3)特定的多肽(甘丙素和神经肽Y0)显著上调输入到发育中的脑干复合体。Y)在存活的V神经节细胞及其中央轴突中，在轴浆运输减弱或离子受损后，与中枢触觉相关的模式的丧失。这项应用中的实验将测试我们的工作假说以及这些关于在将长春花碱应用于离子后导致新生大鼠中枢V型模式丧失的机制的其他可能性。