The neuropeptidergic connectome of Caenorhabitis elegant
Caenorhabitis 优雅的神经肽能连接组
基本信息
- 批准号:10202772
- 负责人:
- 金额:$ 47.98万
- 依托单位:
- 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 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAllelesAnatomyAnimalsBehaviorBiological AssayBiological ModelsBrainCaenorhabditis elegansCellsChemical SynapseCommunicationCommunitiesComplexDataDiffuseDistalElectrical SynapseEnzymesGenesGenomeGoalsHermaphroditismHumanIn VitroIndividualKnowledgeLigandsMapsMass Spectrum AnalysisMethodsMicroscopyNematodaNervous system structureNeuronsNeuropeptide ReceptorNeuropeptidesNeurosciencesOrganismPathway interactionsPatternPhenotypeReceptor ActivationReportingResolutionSignal PathwaySignal TransductionSiteSourceStructureSynapsesSynaptic TransmissionValidationbaseconnectomeinformation processinginsightmalemutantneuroregulationnovelreceptorsexsexual dimorphismtooltransmission process
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.
项目概要
“连接组”描述了大脑的完整突触接线图。
阐明任何动物大脑以及最终人类大脑的连接组
对我们对大脑功能的理解产生巨大影响,并构成了
21 世纪神经科学的中心目标,类似于努力组装完整的
当前的连接组学工作集中于确定基因组序列。
大脑中神经元之间的解剖学突触连接,从而完全
忽略神经通讯中可能同样重要但又不重要的方面
未被解剖学联系捕获:神经调节通讯
神经肽及其同源受体通常是神经肽能通讯。
非突触的,即神经肽通常从非突触位点和同源释放
神经肽受体通常位于远离同源源的地方
而一些神经肽及其受体的重要性。
在控制行为方面受到广泛赞赏,神经肽能的使用程度
动物神经中的每个神经元的信号传导才刚刚开始被充分认识。
现在认为该系统表达至少一种神经肽,但是
这些神经肽能信号的通讯尚未被理解
映射,从而加深我们对神经系统信息流的理解
仍然有限。我们在这里建议使用秀丽隐杆线虫作为模型系统来建立
第一个全面的神经肽能连接组 线虫的简单性。
神经系统可以进行如此全面的分析,重要的是,
允许将神经肽能连接组与完全建立的神经肽能连接组进行比较
根据初步数据,我们期望描述“多层”。
连接体”具有本质上不同的信息流路径,以及不同的
和类似的拓扑特征,我们将通过(1)来实现构建这样的连接组。
通过体外受体激活全面定义配体/受体对
(2)定义所有神经肽和神经肽的表达模式
受体编码基因,(3)将这些数据合成到神经肽能网络中
并通过计算将该网络的拓扑结构与突触进行比较
连接网络和(4)对特定的功能进行初步功能验证
该网络的节点和边。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
System-wide mapping of peptide-GPCR interactions in C. elegans.
线虫中肽-GPCR 相互作用的全系统图谱。
- DOI:
- 发表时间:2023-09-26
- 期刊:
- 影响因子:8.8
- 作者:Beets, Isabel;Zels, Sven;Vandewyer, Elke;Demeulemeester, Jonas;Caers, Jelle;Baytemur, Esra;Courtney, Amy;Golinelli, Luca;Hasakioğulları, İlayda;Schafer, William R;Vértes, Petra E;Mirabeau, Olivier;Schoofs, Liliane
- 通讯作者:Schoofs, Liliane
Physiological insight into the conserved properties of Caenorhabditis elegans acid-sensing degenerin/epithelial sodium channels.
对秀丽隐杆线虫酸敏感简并蛋白/上皮钠通道保守特性的生理学见解。
- DOI:
- 发表时间:2023-05
- 期刊:
- 影响因子:0
- 作者:Kaulich, Eva;McCubbin, Patrick T N;Schafer, William R;Walker, Denise S
- 通讯作者:Walker, Denise S
The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.
DEG/ENaC 家族的多样化功能:将遗传和生理见解联系起来。
- DOI:
- 发表时间:2023-05
- 期刊:
- 影响因子:0
- 作者:Kaulich, Eva;Grundy, Laura J;Schafer, William R;Walker, Denise S
- 通讯作者:Walker, Denise S
A Novel and Functionally Diverse Class of Acetylcholine-Gated Ion Channels.
一类新颖且功能多样的乙酰胆碱门控离子通道。
- DOI:
- 发表时间:2023-02-15
- 期刊:
- 影响因子:0
- 作者:Hardege, Iris;Morud, Julia;Courtney, Amy;Schafer, William R
- 通讯作者:Schafer, William R
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{{ truncateString('Isabel Beets', 18)}}的其他基金
The neuropeptidergic connectome of Caenorhabitis elegant
Caenorhabitis 优雅的神经肽能连接组
- 批准号:
9792310 - 财政年份:2018
- 资助金额:
$ 47.98万 - 项目类别:
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