REGULATION OF NEURITE OUTGROWTH AND CONNECTIVITY

神经突生长和连接的调节

• 批准号: 3477289
• 负责人: CHRISTOPHER S COHAN
• 金额: $ 8.27万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3477289
• 关键词: Gastropoda; axon; calcium; electrophysiology; growth cones; neural information processing; neuroanatomy; neurogenesis; neuronal guidance; neurons; neurotrophic factors; synapses; tissue /cell culture; voltage /patch clamp

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.

电活动在交流中起着基本作用 沿着神经细胞。 长期以来一直认为电活动 在神经元形式的控制中可能发挥更广泛的作用 和连通性。 最近的演示 潜在抑制神经突生长现在提供了概念 这些无处不在的信号可以直接影响这些无处不在的链接 神经元结构和神经回路的形成。 目的 该提案的内容是确定电活动在 调节神经元的形态和连通性，并表明 这些作用可能是通过钙变化介导的 锥。 特别注意电活动的方式 调节延长的尖端的生长锥运动 神经突。 这些实验利用了高分辨率的系统 从蜗牛热瘤中鉴定出的神经元是独特的 以其正常形态（生物物理学）的特征 属性，以及与其他神经元的连接。 细胞体 鉴定的神经元将从其正常中单独删除 神经节环境并将其放置在细胞培养中以促进 神经突的定量空间和时间测量 出生。 细胞体将直接刺激 以及对大生长锥的影响 该物种将进行定量评估以测试如何：1） 电信号的综合特性会影响生长和 神经元的最终形态，2）神经中的电信号 电路可能对全球和局部控制神经元控制 形态学，3）电活动会影响突触发生，4） 生长锥钙的变化可能介导这些作用。 这些发现将在神经元结构和 功能。 他们将洞悉神经元的调节 建立的建筑和连通性 成人神经元电路。