VISUAL SYSTEM DEVELOPMENT AND SYNAPTOGENESIS

提出的研究试图阐明控制数量和 光感受器突触的定性成分。一个主要目标是 了解多接触突触组装的控制(双联体， 三合会等)从对它们正常发育的详细了解 序列，并通过对数字、大小或 他们的蜂窝参与者的组合。为此，光感受器 蝇类和果蝇第一视神经束盒内的突触 已被选为型号，因为每个墨盒都包含一个小的， 已识别的神经元的固定集合。具体目标是：(A) 对所有元素的完整连接矩阵进行分析 来自序列EM的墨盒。马斯卡特别感兴趣的是 相互连接的前向和反馈突触的数量 元素，需要考虑前和前两个阶段的特定神经元 突触后在突触发生中的作用。对果蝇的分析是 没有严重的先例，并将作为基线信息，从 分析有连通性缺陷的视觉突变。(B)审查 突触发生过程中神经元的组合偏好 扰动的类型。激光诱导的发育期或成体的缺失 板层将导致一个或多个突触后细胞的丢失，以测试 增加、删除或替换突触后的机会 光感受器四分体突触的伙伴。类似的影响 还将在果蝇突变体的墨盒中检查缺失情况， VAM，在成人突触后神经元中的一个或两个 以可预测的时间进程经历退化。(C)审查 两项研究中突触发生的定量方面：关于 对蝇类感光细胞突触频率的视觉体验 采用单断面定量EM分析方法进行研究。考虑到 Synapse信号对比，闪烁的灯光效果会 检查过了。其次，对不同的突触间距进行分析 从连续EM和计算机重建正常的发育年龄 光感受器终末和突触后树突，以观察 突触发生与树突形态发生的关系。 之所以在这里提出研究，是因为他们的目标是产生一个基本的模型 适用于多接触突触的突触发生，如二联体和 三合会，应该有助于对微扰的一般理解 在疾病状态下，突触在 发展。

The studies proposed seek to elucidate rules controlling the number and qualitative composition of photoreceptor synapses. A major objective is to understand the control of the assembly of multiple-contact synapses (dyads, triads, etc.) from a detailed knowledge of their normal development sequence and through controlled alterations either to the number, size or combination of their cellular participants. For this, the photoreceptor synapses in cartridges of the first optic neuropile of Musca and Drosophila have been chosen as a model, since each cartridge incorporates a small, fixed set of identified neurons. Specific objectives are: (a) to undertake an analysis of the complete connectivity matrix of all elements of the cartridge from serial EM. Of particular interest for Musca are the number of forward vs feedback synapses between reciprocally-connected elements, needed to consider a particular neuron in both pre- and postsynaptic roles during synaptogenesis. The analysis in drosophila is without serious precedent and will serve as baseline information from which to analyze visual mutants with connectivity defects. (b) to examine the combinatorial preferences of neurons during synaptogenesis, following two types of perturbation. Laser-induced deletions of the developing or adult lamina will procure the loss of one or more postsynaptic cells, to test the opportunity for additions, deletions, or substitutions of postsynaptic partners at photoreceptor tetrad synapses. The effects of similar deletions will also be examined in cartridges of the Drosophila mutant, Vam, where one or both of a pair of postsynaptic neurons in the adult undergo(es) degeneration with a predictable time-course. (c) to examine quantitative aspects of synaptogenesis in two studies: on the effects of visual experience on the frequency of photoreceptor synapses in Musca, to be studied using single-section quantitative EM analysis. Given that the synapse signals contrast, the effects of flickering lights will be examined. Secondly, synapse spacing will be analyzed at different developmental ages, from serial EM and computer reconstruction of normal photoreceptor terminals and postsynaptic dendrites, to examine the relationship between synaptogenesis and dendritic morphogenesis. The studies proposed here because they aim at producing a basic model of synaptogenesis applicable to multiple-contact synapses, such as dyads and triads, should contribute to a general understanding of the perturbations in disease states to which synapses are susceptible during their development.