AGE, AXON INJURY AND MOTOR NEURON SYNAPTOLOGY

当运动神经元的轴突受到损伤时，神经元会失去大部分 中枢传入联系。当发生以下情况时，这些中心变化会发生逆转 轴突恢复适当的外周接触。这项提议旨在 观察面部运动损伤后突触关系的变化 幼年(3月龄)面神经挤压伤后的神经元 和中年(15月龄)大鼠。这种分析的模型是理想的 因为面部神经核是运动神经元的同质群体， 它的传入神经有很好的特征，它不会失去神经元。 随着年龄的增长。我们的初步研究表明，恢复 在老年动物中，中枢传入联系可能不完整 在外周神经再支配之后。 将使用形态计量学和电子技术对面部运动核进行检查 显微镜免疫细胞化学法确定终末的身份 表现为类GABA、类5-羟色胺和类去甲肾上腺素 免疫反应性。精细结构形态测量的标准程序 (包括从连续薄片重建)将建立一个 正常轴突的所有形态类型的“目录” 面部神经核。在轴突挤压后，被识别的 码头的特点将是它们的命运和恢复，就像 神经元和神经胶质细胞的反应。此外, 放射自显影分析将确定损失的动力学和 突触后GABA-A、5-羟色胺IA和2、β-受体的恢复 肾上腺素能受体配体结合。受体动力学将与 5-羟色胺和去甲肾上腺素摄取部位与突触前的结合 感受器。这些研究将在以下结果之间建立一座桥梁 解剖学、免疫细胞化学和药理学方法研究 增龄对运动神经元反应影响的研究 致伤。 鉴于这些突触连接和受体在脑内的关键作用 神经元的兴奋性和钙离子的动员 了解年龄增长如何损害神经元的能力 从周围神经损伤中恢复。这样的理解很重要 对旨在改善神经的治疗干预的发展 再生。

When the axon of a motor neuron is injured, the neuron loses much of its central afferent connectionns. These central changes are reversed when the axons restore appropriate peripheral contacts. This proposal aims to examine the changing synaptic relationships of injured facial motor neurons following crush injury of the facial nerve in young (3 month) and middle aged (15 month) rats. The model for this analysis is ideal because the facial nucleus is a homogeneous population of motor neurons, its afferent innervation is well characterized, and it loses no neurons with advancing age. Our preliminary studies suggest that recovery of central afferent connections may be incomplete in older animals following peripheral reinnervation. The facial motor nucleus will be examined using morphometry and electron microscope immunocytochemistry to determine the identity of terminals showing GABA-like, serotonin-like and noradrenalin-like immunoreactivity. Standard procedures of fine structure morphometry (including reconstruction from serial thin sections) will establish a "catalog" of all morphological types of axon boutons in the normal facial nucleus. Following axon crush the response of the identified terminals will be characterized as to their fate and recovery, as will the response of the neurons and neuroglial cells. In addition, autoradiographic analysis will determine the dynamics of loss and recovery of postsynaptic GABA-A, serotonin IA and 2, and Beta- adrenoceptor ligand binding. Receptor dynamics will be correlated with binding to serotonin and noradrenalin uptake sites and presynaptic receptors. These studies will establish a bridge between the results of anatomical, immunocytochemical and pharmacological approaches to the investigation of the effects of advancing age on motor neuron response to injury. Given the crucial role of these synaptic connections and receptors in neuronal excitability and calcium mobilization it is important to understand how advancing age compromises the ability of neurons to recover from peripheral nerve injury. Such understanding is important to the development of therapeutic intervention designed to improve nerve regeneration.