REGULATION OF NEURITE OUTGROWTH AND CONNECTIVITY

电活动在交流中起着基础性作用 沿着神经细胞。长期以来，人们一直认为电活动 可能在控制神经元形态方面发挥更广泛的作用 和连通性。最近的行动表明， 抑制轴突生长的电位现在提供了概念性的 这些无处不在的信号可以直接影响 神经结构和神经回路的形成。目标 该提案的目的是确定电活动在 调节神经元的形态和连通性，并表明 这些影响可能是通过生长过程中钙离子的变化来实现的。 圆锥体。特别注意电活动是如何 调节生长锥在伸长顶端的运动 神经突起。这些实验利用了一种高分辨率系统 从蜗牛海鞘瘤中鉴定出独特的神经元 以它们的正常形态、生物物理 属性，以及与其他神经元的联系。胞体 已识别的神经元将从其正常状态中单独移除 神经节细胞环境和放置在细胞培养中便于 轴突的空间和时间定量测量 外延生长。细胞体将直接受到电刺激 以及对大型生长锥体的影响 将对该物种进行定量评估，以测试如何：1) 电信号的综合特性影响生长和 神经元的最终形态，2)神经中的电信号 电路可以对神经元进行全局和局部控制 形态，3)电活动影响突触发生，4) 生长锥体内钙离子的变化可能介导这些效应。 这些发现将在神经元结构和 功能。他们将提供对神经元调节的洞察力 架构和连接性是建立 成人神经元回路。

Electrical activity plays a fundamental role in communication along nerve cells. It has long been thought that electrical activity might play a much broader role in the control of neuronal form and connectivity. The recent demonstration that action potentials inhibit neurite outgrowth now provides the conceptual link whereby these ubiquitous signals can directly influence neuronal structure and the formation of neural circuits. The aims of the proposal are to determine the role of electrical activity in regulating neuronal morphology and connectivity and to show that these effects may be mediated by calcium changes in growth cones. Specific attention is given to how electrical activity regulates the movements of growth cones at the tips of elongating neurites. These experiments utilize a high resolution system of identified neurons from the snail Helisoma which are uniquely characterized in terms of their normal morphology, biophysical properties, and connections with other neurons. Cell bodies of identified neurons will be individually removed from their normal ganglionic environment and placed in cell culture to facilitate quantitative spatial and temporal measurements of neurite outgrowth. Cell bodies will be electrically stimulated directly and the effects on the large growth cones that are characterized of this species will be quantitatively assessed to test how: 1) integrative properties of electrical signals affect outgrowth and the final morphology of neurons, 2) electrical signals in neural circuits may exert both global and local control over neuronal morphology, 3) electrical activity affects synapotogenesis, and 4) changes in growth cone calcium may mediate these effects. These findings will establish a link between neuronal structure and function. They will provide insight into the regulation of neuronal architecture and connectivity which underlie the establishment of adult neuronal circuits.