SYNAPTOGENESIS IN DEVELOPMENT AND SYNAPTIC PLASTICITY

发育中的突触发生和突触可塑性

基本信息

批准号：
6187895
负责人：
DANIEL J GOLDBERG
金额：
$ 22.55万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-04-01 至 2002-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6187895
关键词：
Aplysia actins afferent nerve cell motility growth cones motor neurons nervous system regeneration neural plasticity neuroregulation synaptogenesis tissue /cell culture video microscopy

项目摘要

DESCRIPTION: The long-term objective of the work is to contribute to an understanding of subcellular and molecular events underlying synapse formation during development, regeneration and long-term synaptic plasticity. The specific aim here is to assess the importance of the regulation of actin-based motility in synapse formation. It is hypothesized that, during development and regeneration, suppression of actin-based motility is a key early step in the interaction of the tip of a growing axon with the site at which it will form a synapse. This hypothesis will be tested using models of two different types of synapse formation. One is of the type in which the ingrowing axon stops at a site and forms a single synapse. Here, high resolution VEC-DIC microscopy will be used to determine the mechanism whereby a peptide concentrated at the neuromuscular junction, LRE, specifically acts on the growth cone of the motor neuron to stop axon growth. The other model is of the type in which multiple, spatially discrete en passant synapses are formed by the axon growing along its target. Here, video-intensified fluorescence microscopy will be used to observe the interaction in culture of growth cones of an identified Aplysia sensory neuron with specific target sites on its motor neuron partner. Long-term increases in adult synaptic efficacy may be caused by the formation of new synapses. In at least some cases this is associated with the growth of axonal arbor. It is hypothesized that induction of actin-based motility is the first step in this growth. This hypothesis will be tested using video-intensified fluorescence microscopy with the Aplysia sensory neuron/motor neuron coculture, which displays such plasticity. An identification of specific changes in motility should point to specific molecular targets within the presynaptic element for signals regulating synapse formation during development, regeneration and synaptic plasticity.

描述：这项工作的长期目标是为了解突触背后的亚细胞和分子事件发育、再生和长期突触过程中的形成可塑性。这里的具体目的是评估突触形成中基于肌动蛋白的运动的调节。据推测在发育和再生过程中，基于肌动蛋白的抑制运动是生长轴突尖端相互作用的关键早期步骤与它将形成突触的位置。这个假设将是使用两种不同类型的突触形成模型进行测试。其一是属于向内生长的轴突停在一个位置并形成单个轴突的类型突触。在这里，高分辨率 VEC-DIC 显微镜将用于确定肽集中在神经肌肉接头处的机制， LRE，专门作用于运动神经元的生长锥以阻止轴突生长。另一种模型是多重、空间的模型。离散的突触是由轴突沿着其生长形成的目标。在这里，视频增强荧光显微镜将用于观察已识别的海兔生长锥培养物中的相互作用感觉神经元在其运动神经元伙伴上具有特定的目标位点。成人突触功效的长期增加可能是由新突触的形成。至少在某些情况下，这与轴突乔木的生长。据推测，诱导基于肌动蛋白的运动是这种生长的第一步。这个假设将使用海兔视频增强荧光显微镜进行测试感觉神经元/运动神经元共培养，表现出这种可塑性。运动性具体变化的识别应指出突触前元件内信号的特定分子靶标在发育、再生和突触过程中调节突触形成可塑性。