Identifying mRNAs associated with a synaptogenic calcium-mediated pathway

电压门控钙通道是驱动突触的引擎。它们是囊泡胞吐所必需的，现在很明显，这些分子对神经网络中基础变化的形成、维持、适应和消除的动力学至关重要。因此，随着我们研究这些分子及其作用方式，我们将对神经系统的基本组装有更清晰的了解。VGCC与人类疾病和紊乱有关，我们的目标是进一步了解这些蛋白质如何促进神经元发育。使用突变失活或过度活跃的突触VGCC的动物，我们将获得转录组图谱，以识别受VGCC功能状态转录调控的基因。然后，我们将以这些基因为靶点，通过RNAi来寻找有助于VGCC依赖的突触添加的分子。最后，我们将试图可视化在突触发育过程中修改细胞内钙水平与突触特定变化之间的关系时，钙可能是如何动态变化的。线虫神经肌肉系统的组织结构为研究发育提供了强大的遗传和细胞生物学模型。初级运动神经元与脊椎动物中枢神经系统神经元有许多相似之处，而脊椎动物中枢神经系统神经元在体内更难研究。线虫可能为体内这些类型突触的形成和间隔的机制提供重要的见解。

Voltage-gated calcium channels are the engines that drive the synapse. They are required for vesicle exocytosis, and it is now clear that these molecules are critically important to the dynamics of formation, maintenance, adaption and elimination that underlie changes in neural networks. Therefore, as we study these molecules and their mode of action, we will gain a much clearer understanding of the basic assembly of the nervous system. VGCCs have been linked to human diseases and disorders, and our goal is to further the understanding of how these proteins contribute to neuronal development. Using animals that have mutations that inactivate or hyperactive synaptic VGCCs we will obtain transcriptome profiles to identify genes that are transcriptionally regulated by VGCC functional status. We will then target those genes for knockdown by RNAi to find molecules that contribute to VGCC-dependent synapse addition. Finally we will seek to visualize how calcium may be dynamic during times when synapses are being modified during development to correlate intracellular levels of calcium with specific changes in synapses. The organization of the C. elegans neuromuscular system provides a powerful genetic and cell biological model to study development. The primary motorneurons have many similarities to vertebrate CNS neurons, which are more difficult to study in vivo. C. elegans may provide important insights into the mechanisms that underlie the formation and spacing of these types of synapses in vivo.