DEVELOPMENT OF SENSORY-MOTONEURON SYNAPSES

感觉运动神经元突触的发育

• 批准号: 3407721
• 负责人: Lea Ziskind-Conhaim
• 金额: $ 16.49万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3407721
• 关键词: action potentials; afferent nerve; axon reaction; cell differentiation; central nervous system; dorsal root; electron microscopy; electrophysiology; embryo /fetus; evoked potentials; immunocytochemistry; innervation; laboratory rat; mammalian embryology; microscopy; motor neurons; neural information processing; neural inhibition; neural initiation; neurogenesis; neuromuscular function; neuromuscular junction; neuromuscular transmission; neuronal guidance; neuropharmacology; organ culture; peripheral nervous system; sensorimotor system; sensory deprivation; spinal cord injury; spinal nerves; synapses; synaptogenesis; ventral roots

The objectives of this proposal are to characterize the changes in electrical and pharmacological properties of spinal motoneurons during embryonic development and after injury. We will determine: 1) the influence of newly formed central and peripheral synapses on motoneuron properties, and 2) the effects of sensory deprivation and axotomy on motoneuron differentiation. These studies will be carried out using two preparations: 1) isolated lumbar segments of rat spinal cord, in which functional sensorimotor pathways are preserved for at least 9 hours, and 2) spinal cord-muscle explants in which motoneurons are viable for 4-6 days. The isolated spinal cord of rat embryos is particularly suitable for studying neural and synaptic responses to known concentrations of ions and drugs. We have been using this preparation to study the pattern and time course of formation of excitatory and inhibitory synapses in spinal cord, and to examine the effects of the new synapses on motoneuron properties. The results of the proposed studies will establish the pattern of motoneuron differentiation in vivo, and will guide our future studies on motoneuron development in organ culture. Isolated segments of thoracic spinal cord with their associated intercostal muscles will be maintained in vitro for a period of several days. The advantage of using spinal cord-intercostal muscle explants are: 1) motoneurons are cultured in continuity with the muscles they normally innervate in vivo, and 2) we have previously described the chronology of changes that occur during development of intercostal neuromuscular junctions in vivo and in organ culture. We will thus be able to correlate these changes with differentiation of motoneurons that innervate these muscles. Maintaining these explants in a controlled environment provides valuable means for determining the extracellular factors that influence motoneuron properties and the formation of specific central neural pathways. Acquisition of motoneuron specific characteristics arises from interactions between intrinsic instructions and extracellular factors, but little is known about their relative contributions to differentiation of mammalian neurons. The proposed studies will extend our understanding about the way functional neural circuits develop, and the effects of newly formed pathways on neuron differentiation. This understanding should provide insight into mechanisms underlying long-term interactions between neurons in the central nervous system.

该提案的目标是表征 脊柱运动神经元的电气和药理特性 胚胎发育和受伤后。 我们将确定：1） 新形成的中央和周围突触对运动神经元的影响 特性和2）感觉剥夺和轴切开术对 运动神经元分化。 这些研究将使用两种制剂进行：1）孤立 大鼠脊髓的腰部段，其中功能性感觉运动 途径至少保存9小时，2）脊髓肌肉 运动神经元可行4-6天的外植体。 孤立的脊柱 大鼠胚胎的绳索特别适合研究神经和 对已知浓度的离子和药物的突触反应。 我们去过 使用此准备工作来研究形成的模式和时间过程 脊髓中的兴奋性和抑制性突触，并检查 新突触对运动神经元性质的影响。 结果 拟议的研究将建立运动神经元分化的模式 体内，将指导我们未来关于运动神经元发展的研究 器官文化。 胸脊髓的孤立段 相关的肋间肌肉将在体外保持一段时间 几天。 使用脊髓斜切肌肉的优点 外植体是：1）运动神经元与肌肉的连续性培养 它们通常在体内支配，2）我们先前已经描述了 肋间发展过程中发生的变化的年表 体内和器官培养中的神经肌肉连接。 因此，我们将能够 将这些变化与运动神经元的分化相关联 支配这些肌肉。 在受控的 环境提供了确定细胞外的有价值的手段 影响运动神经元特性和特定形成的因素 中央神经通路。 动作神经元特定特征的获取是由相互作用引起的 在内在指示和细胞外因素之间，但几乎没有 知道他们对哺乳动物分化的相对贡献 神经元。 拟议的研究将扩展我们对方式的理解 功能性神经回路发展，新形成的影响 神经元分化的途径。 这种理解应该提供 深入了解神经元之间长期相互作用的机制 在中枢神经系统中。