DEVELOPMENT OF SENSORY/MOTOR SYNAPSES IN THE SPINAL CORD

描述（来自申请人摘要的逐字）： 神经系统依赖于高度特异性的 轴突投射和神经细胞之间的突触连接。了解 这是如何发生的，本提案采取的方法是研究 在脊髓中发育一组特征良好的突触通路 脊髓，那些参与肌肉长度和张力的反射控制。 供应肌梭的感觉神经元（Ia传入）主要是 对肌肉长度敏感;它们投射到脊髓中， 与运动神经元的特定子集的单突触连接。其他 本体感觉神经元（Ib传入），供应高尔基腱器官 对活跃的肌肉张力敏感的神经元， 与运动神经元，但这些连接是介导的多突触。这些 问题将解决使用分离的新生小鼠脊髓 准备.这种制备的一个主要优点是， 本体感受传入（Ia和Ib神经元）可以被选择性地刺激， 细胞内记录可以从功能上鉴定的运动神经元进行。 转基因和基因敲除小鼠的可用性使得有可能测试 特定分子和细胞类型在产生这些特定模式中的作用 连接。 这里提出的实验研究这些途径中的每一个是如何发展的。为 从肌梭的Ia途径，我们将重点关注的作用， 纺锤体本身为Ia提供营养支持和指导性指导 感觉神经元，无论是在胚胎发育和新生儿 突触连接仍在形成的时期。我们还将测试 转录因子的ETS基因家族参与帮助指定 Ia感觉运动突触的模式对于多突触Ib通路，我们 将确定预测是否从一开始就具体发展， 连接，或者如果突触模式被重塑，就像在大脑的其他部分一样。 神经系统虽然这项提案中的实验仅限于 正常的发展，很可能涉及的机制的知识， 在发育过程中形成脊髓通路将有助于 制定脊髓损伤后重建这些通路的策略， 损伤

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.