Cell Interactions in Synapes Formation and Function

描述（由申请人提供）：本研究的长期目标 该计划旨在阐明参与的细胞和分子机制， 突触接触的形成和功能。现时的建议 着重于细胞粘附在三种主要突触形成中的作用， 特化：突触前末梢、活动区和躯体棘。的 一个主要的假设是，发展中国家介导的粘合剂联系 细胞-细胞和细胞-基质相互作用是结构所必需的。 突触的组织和功能。此外，精确控制 突触的结构修饰需要表面粘附 对生理刺激的反应。 利用鸡睫状神经节的萼型突触作为一种 实验模型系统和逆转录病毒系统诱导分子 在发展过程中的扰动，这项研究将集中在两个作用 粘附分子家族，即钙粘蛋白和整联蛋白。这些 分子由于其突出的粘附活性而被选择， 睫状神经节表达模式。 N-cadherin和整合素（β 1和β 4）在结构中的作用 突触的组织将通过扰动它们的粘合剂来研究。 具有野生型和突变分子的特性， 方面的影响.将评价干扰细胞粘附的后果 形态学上，通过分析突触的结构， 共聚焦和电子显微镜水平，并通过评估功能 电生理学的突触传递的功效和特性 睫状神经元电流的变化。 从这项研究中获得的信息将有助于更好地了解 突触发生和突触功能的结构要求。作为 各种精神和神经疾病被认为是由 突触功能障碍，这些研究将有助于基础知识， 阐明神经病理学的细胞和分子机制 条件

DESCRIPTION (provided by applicant): The long-term goal of this research program is to elucidate the cellular and molecular mechanisms that participate in the formation and function of a synaptic contact. The present proposal focuses on the role of cell adhesion in the formation of three major synaptic specializations: presynaptic terminals, active zones, and somatic spines. The primary hypothesis is that the development of adhesive linkages mediated by cell-cell and cell-matrix interactions are required for the structural organization and function of the synapse. In addition, a precise control of surface adhesion is needed for the structural modification of the synaptic junction in response to physiological stimuli. Utilizing the calyx-type synapse of the chick ciliary ganglion as an experimental model system and a retroviral system to induce molecular perturbations during development, this study will focus on the role of two families of adhesion molecules, namely the cadherins and the integrins. These molecules have been selected because of their prominent adhesive activity and expression pattern in the ciliary ganglion. The role of N-cadherin and integrins (beta1 and beta4) in the structural organization of the synapse will be investigated by perturbing their adhesive properties with wild type and mutated molecules that exert dominant negative effects. The consequences of interfering with cell adhesion will be evaluated morphologically, by analyzing the structure of the synapse at the light confocal and electron microscopic level, and functionally by assessing electrophysiologically the efficacy of synaptic transmission and the properties of the electrical currents of the ciliary neurons. The information gained from this study will lead to a better understanding of synaptogenesis and the structural requirements for synaptic function. As a variety of psychiatric and neurological disorders are believed to arise from synaptic malfunction, these studies will contribute basic knowledge toward elucidation of cellular and molecular mechanisms underlying neuropathological conditions.