The neuropeptidergic connectome of Caenorhabitis elegant

项目摘要 “Connectome”描述的是大脑完整的突触接线图。这个 阐明任何动物大脑的连接体，最终，人类大脑将 对我们对大脑功能的理解有巨大的影响，并构成了 21世纪神经科学的中心目标，类似于组装完整的 基因组序列。目前的连接努力集中在确定 大脑中神经元之间的解剖突触连接，从而完全 忽略神经元通信的一些方面，这些方面可能同样重要，但 未被解剖连接捕获：神经调节性交流 神经肽及其同源受体。神经肽能通讯通常是 非突触，即神经肽通常从非突触部位和同源部位释放 神经肽受体通常位于同源词来源的远端 神经肽。而一些神经肽及其受体的重要性 在控制行为方面，神经肽能的使用程度是很好的 信号才刚刚开始被充分理解。动物身上的每一个神经细胞都很紧张 系统现在被认为至少表达一种神经肽，但 这些神经肽能信号的交流还没有被理解。 因此，我们对神经系统中的信息流的理解 仍然是有限的。我们建议在这里以线虫作为模式系统来建立 第一个全面的神经肽能连接体。线虫的简单 神经系统允许进行如此全面的分析，重要的是， 允许将神经肽能连接体与完全已建立的 突触连接体。根据初步数据，我们预计将描述一个“多层 连接体“具有明显不同的信息流路径以及不同的 和相似的拓扑特征。我们将通过(1)实现建立这样一个连接体 通过体外受体激活全面确定配体/受体对 分析，(2)确定所有神经肽和神经肽的表达模式 受体编码基因，(3)将这些数据合成一个神经肽能网络 并通过计算将这个网络的拓扑与突触进行比较 连通性网络和(4)进行具体的初步功能验证 此网络的节点和边缘。

Project Summary A “connectome” describes the complete synaptic wiring diagram of a brain. The elucidation of the connectome of any animal brain and, ultimately, the human brain will have a tremendous impact on our understanding of brain function and constitutes a central goal of 21st century neuroscience, akin to the efforts to assemble the complete sequence of genomes. Current connectomic efforts are focused on determining the anatomical synaptic connections between neurons in a brain, thereby completely ignoring aspects of neuronal communication that are likely of equal importance but are not captured by anatomical connections: Neuromodulatory communication by neuropeptides and their cognate receptors. Neuropeptidergic communication is usually non-synaptic, i.e. neuropeptides are often released from non-synaptic sites and cognate neuropeptide receptors are often located distal from the source of the cognate neuropeptide. While the importance of a number of neuropeptides and their receptors in controlling behavior are well appreciated, the extent of usage of neuropeptidergic signaling is only beginning to be fully appreciated. Every neuron in an animal nervous system is now thought to express at least one neuropeptide, but the pathways of communication of these neuropeptidergic signals have not been comprehensibly mapped and, hence, our understanding of information flow in the nervous system remains limited. We propose here to use C. elegans as a model system to establish the first comprehensive neuropeptidergic connectome. The simplicity of the C. elegans nervous system allows to undertake such a comprehensive analysis and, importantly, allows to compare a neuropeptidergic connectome to that of the completely established synaptic connectome. Based on preliminary data we expect to describe a “multilayer connectome” with substantially distinct pathways of information flow, as well as distinct and similar topological features. We will achieve to build such a connectome through (1) comprehensively defining ligand/receptor pairs through in vitro receptor activation assays, (2) defining the expression patterns of all neuropeptide and neuropeptide receptor encoding genes, (3) synthesizing these data into a neuropeptidergic network and computationally comparing the topology of this network to the synaptic connectivity network and (4) undertaking a preliminary functional validation of specific nodes and edges of this network.