Cellular and molecular mechanisms of neuronal remodeling in healthy tissue

项目摘要/摘要 在成人神经系统中，周围感觉神经元维持适当的神经支配模式。 尽管靶上皮细胞不断更新，但它们仍能支配细胞。这项研究的目的是阐明 控制健康组织中外周神经元可塑性的基本神经机制。该项目 重点介绍了默克尔细胞-轴突复合体，这是由表皮默克尔组成的高敏感度触摸感受器 由有髓(Aβ)感觉传入支配的细胞。这些有辨别力的触摸感受器富含 指尖、胡须毛囊和毛茸茸的皮肤触碰穹顶。在小鼠身上，皮肤会发生显著的变化 在毛发生长周期中的厚度和硬度，这在整个成年期重复。这些靶器官 伴随着改变的是默克尔细胞外周轴突复杂性的快速可塑性 传入器。这一应用的中心假设是，决定神经元重塑的内在路径 损伤后还支配着健康组织的结构可塑性，这会导致整个组织的行为相关变化 感官模式。这一假设将使用转基因小鼠模型的组合进行验证， 神经解剖学和三维神经元示踪，活体细胞成像和感觉行为测试。 目标1将测试是否涉及轴突损伤后介导轴突变性和再生的通路 在健康组织的传入重塑中。这个目标将评估在定义的神经元形态上的差异 缺乏干扰损伤诱导信号通路的基因的转基因小鼠的毛发周期阶段。目标2 将使用小鼠行为分析来测试体感传入是否调节不同的感觉 模式的重塑是并行的。这些研究将确定神经细胞重塑的功能后果。 健康组织以及调节结构可塑性的细胞和分子机制。

PROJECT SUMMARY/ABSTRACT In the adult nervous system, peripheral sensory neurons maintain appropriate innervation patterns despite continual turnover of the target epithelia they innervate. The goal of this research is to elucidate fundamental neuronal mechanisms that govern plasticity of peripheral neurons in healthy tissue. The project focuses on Merkel cell-neurite complexes, which are high acuity touch receptors composed of epidermal Merkel cells innervated by myelinated (Aβ) sensory afferents. These discriminative touch receptors are enriched in fingertips, whisker follicles and touch domes in hairy skin. In mice, skin goes through marked changes in thickness and stiffness during the hair growth cycle, which repeats throughout adulthood. These target-organ changes are accompanied by rapid plasticity in the complexity of peripheral axonal arbors of Merkel-cell afferents. This application's central hypothesis is that the intrinsic pathways that dictate neuronal remodeling after injury also govern structural plasticity in healthy tissue, which causes behaviorally relevant changes across sensory modalities. The hypothesis will be tested using a combination of transgenic mouse models, quantitative neuroanatomy and three-dimensional neuronal tracing, in vivo, live-cell imaging and sensory behavioral tests. Aim 1 will test whether pathways that mediate axonal degeneration and regrowth after axonal injury are involved in afferent remodeling in healthy tissue. This aim will evaluate differences in neuronal morphology at defined hair cycle stages in transgenic mice lacking genes that interfere with injury-induced signaling pathways. Aim 2 will use mouse behavioral assays to test whether somatosensory afferents that mediate distinct sensory modalities remodel in parallel. These studies will define the functional consequences of neuronal remodeling in healthy tissue as well as cellular and molecular mechanisms that mediate structural plasticity.