DEVELOPMENT OF SENSORY/MOTOR SYNAPSES IN THE SPINAL CORD

描述(逐字摘自申请人摘要)：正确操作 神经系统依赖于高度特异模式的形成 神经细胞之间的轴突投射和突触连接。要理解 这是如何发生的，这项建议采取的方法是研究 脊髓内一组特征明确的突触通路的发育 绳索，那些参与反射控制的肌肉长度和张力。 供应肌梭的感觉神经元(Ia传入)主要是 对肌肉长度敏感；它们投射到脊髓，在那里它们 与运动神经元的特定亚群的单突触联系。其他 供应高尔基体肌腱器官的本体感觉神经元(Ib传入) 对活跃的肌肉张力敏感的，也会建立特定的联系 运动神经元，但这些联系是通过多突触调节的。这些 这些问题将通过分离的新生小鼠脊髓来解决 准备工作。这种制剂的一个主要优点是不同级别的 本体感受性传入(Ia和Ib神经元)可以被选择性地刺激和 细胞内的记录可以从功能上识别的运动神经元进行。 转基因和基因敲除小鼠的出现使测试 特定分子和细胞类型在产生这些特定模式中的作用 联系的人。 这里提出的实验考察了每条途径是如何发展的。为 从肌梭的Ia通路中，我们将重点介绍Ia在肌梭中所起的作用 主轴本身为Ia提供营养支持和指导性指导 胚胎发育和新生儿时期的感觉神经元 突触连接仍在形成的时期。我们还将测试是否 ETS基因家族的转录因子参与了帮助指定 Ia感觉-运动突触的模式。对于多突触Ib途径，我们 将确定预测是否从一开始就特别制定，例如 IA连接，或者如果突触模式像在大脑其他部分一样被重塑 神经系统。尽管这项提案中的实验仅限于 正常发育，很可能是知识所涉及的机制 在发育过程中脊髓通路的形成将有助于 脊髓损伤后重建这些通路的发展策略 受伤。

DESCRIPTION (Verbatim from the Applicant's Abstract): The correct operation of the nervous system depends on the formation of highly specific patterns of axonal projections and synaptic connections among nerve cells. To understand how this occurs, the approach taken in this proposal is to study the development of one well characterized set of synaptic pathways in the spinal cord, those involved in the reflex control of muscle length and tension. Sensory neurons supplying muscle spindles (Ia afferents) are primarily sensitive to muscle length; they project into the spinal cord where they make monosynaptic connections with particular subsets of motoneurons. Other proprioceptive sensory neurons (Ib afferents), supplying Golgi tendon organs that are sensitive to active muscle tension, also make specific connections with motoneurons, but these connections are mediated polysynaptically. These issues will be addressed using the isolated neonatal mouse spinal cord preparation. A major advantage of this preparation is that different classes of proprioceptive afferents (Ia and Ib neurons) can be stimulated selectively and intracellular recordings can be made from functionally identified motoneurons. The availability of transgenic and knock-out mice makes it possible to test the role of specific molecules and cell types in generating these specific patterns of connections. The experiments proposed here examine how each of these pathways develops. For the Ia pathway from muscle spindles, we will focus on the role played by the spindle itself in providing trophic support and instructive guidance for Ia sensory neurons, both during embryonic development and during the neonatal period when synaptic connections are still being formed. We will also test if the ETS gene family of transcription factors is involved in helping to specify the pattern of Ia sensory-motor synapses. For the polysynaptic Ib pathway, we will determine if the projections develop specifically from the outset, as for Ia connections, or if synaptic patterns are remodeled as in other parts of the nervous system. Although the experiments in this proposal are confined to normal development, it is likely that knowledge of the mechanisms involved in the formation of spinal pathways during development will be useful in developing strategies for the reconstruction of these pathways after spinal injury.