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The neuropeptidergic connectome of Caenorhabitis elegant

Caenorhabitis 优雅的神经肽能连接组

基本信息

批准号：
9792310
负责人：
Isabel Beets
金额：
$ 49.03万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2022-06-30
项目状态：
已结题

项目摘要

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.

项目摘要 “连接体”描述了大脑的完整突触接线图。的阐明任何动物大脑的连接体，最终，人类大脑将对我们理解大脑功能有着巨大的影响，这是21世纪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组学工作集中在确定大脑中神经元之间的解剖学突触连接，从而完全忽略了神经元通讯的一些方面，这些方面可能同样重要，不被解剖学连接捕获：神经调节通信神经肽及其同源受体。神经肽能通讯通常是非突触的，即神经肽通常从非突触位点释放，神经肽受体通常位于同源物来源的远端神经肽虽然一些神经肽及其受体的重要性在控制行为方面，神经肽能药物的使用程度信令才刚刚开始被充分理解。动物体内的每一个神经元现在认为系统表达至少一种神经肽，但是这些神经肽能信号的通讯还不能被理解绘制了神经系统中的信息流，仍然有限。我们建议在这里使用C。elegans作为一个模型系统来建立第一个全面的神经肽能连接体。C. elegans 神经系统允许进行这种全面的分析，重要的是，允许将神经肽能连接体与完全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”具有基本上不同的信息流途径，以及不同的和相似的拓扑特征。我们将通过（1）来构建这样一个连接体。通过体外受体活化全面定义配体/受体对测定，（2）确定所有神经肽和神经肽的表达模式受体编码基因，（3）将这些数据合成为神经肽能网络并通过计算将这个网络的拓扑结构与（4）对特定的网络进行初步的功能验证。这个网络的节点和边缘。