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Synaptic target selection in the thermotaxis neural circuit of C. elegans

线虫趋热神经回路中的突触目标选择

基本信息

批准号：
7916364
负责人：
DANIEL A COLON-RAMOS
金额：
$ 30.78万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-12-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7916364
关键词：
Address Affect Afferent Neurons Animals Autistic Disorder Axon Behavior Behavioral Biological Models Brain Caenorhabditis elegans Cells Chemotaxis Cloning Complex Defect Dendrites Development Environment Exhibits Future Genetic Screening Goals Grant Human Imagery Immunoglobulins Interneurons Label Lead Learning Location Molecular Nematoda Neurites Neurodevelopmental Disorder Neurons Pattern Phenotype Play Presynaptic Terminals Proteins Research Research Project Grants Role Schizophrenia Signal Pathway Signal Transduction Site Sorting - Cell Movement Specific qualifier value Specificity Structure Synapses Synaptic Vesicles System Visual Work axon guidance base behavior influence human disease immunoglobulin receptor in vivo insight multidisciplinary mutant neural circuit novel postsynaptic presynaptic programs research study rib bone structure synaptogenesis

项目摘要

The human brain consists of approximately 100 billion neurons, which form over 100 trillion synapses with specific targets. How neurons find the correct targets and how the correct wiring of the brain influences behavior are central questions, and the focus of this proposal. The nematode C. elegans offers an excellent model system to explore how synaptic specificity is achieved in vivo, and how correct synaptic choices influence the formation of neuronal circuits, and behavior. AIY, an important interneuron in the C. elegans brain, receives inputs from multiple sensory neurons to modulate behaviors such as thermotaxis, chemotaxis and learning. During development AIY contacts many neurites, but selects only three neurons (RIA, RIB and AIZ) as its postsynaptic partners. The molecular mechanisms used by AIY to discriminate between potential targets and form functional neuronal circuits are not understood. Here I propose to characterize how synaptogenesis is regulated in the complex environment of the C. elegans brain by studying synaptic formation in the thermotaxis neural circuit. A visual forward genetic screen on AIY synapses has yielded multiple mutants with abnormal synaptic patterns. I will identify AIY synaptic specificity molecules by characterizing these mutants. Initial characterization of one class of mutants indicates that immunoglobulin superfamily protein UNC-40/DCC directs AIY synaptogenesis in a cell autonomous manner. In unc-40 mutant, AIY exhibits normal axon trajectory with abnormal presynaptic locations. UNC-40 localizes to AIY presynaptic sites in wild type animals. Furthermore, mislocalization of UNC-40 leads to ectopic presynaptic terminal formation at the location of mislocalized UNC-40. Further experiments will identify the mechanism by which unc-40 directs synaptic target selection in AIY. Future characterization of mutants with similar AIY phenotype as unc-40 will determine the molecular signaling pathway that leads to correct AIY synaptogenesis. Together our work promises to lend us insights into the molecular components that direct correct synaptogenesis in the C. elegans brain. Altered synaptogenesis might lead to a number of neurodevelopmental disorders and human diseases such as schizophrenia and autism. Understanding correct synaptogenesis should provide insights into how functional neuronal circuits are constructed during development and how the correct formation of these circuits affects behavior.

人脑由大约1000亿个神经元组成，这些神经元形成了超过100万亿个突触特定的目标。神经元如何找到正确的目标以及大脑的正确连接如何影响行为是核心问题，也是这项提案的重点。线虫线虫提供了一种极好的探索突触特异性是如何在体内实现的，以及如何正确选择突触的模型系统影响神经回路的形成和行为。线虫体内重要的中间神经元AIY 大脑，接受来自多个感觉神经元的输入，以调节行为，如热趋化，趋化和学习。在发育过程中，AIY接触许多神经突起，但只选择三个神经元(RIA、RIB和 Aiz(Aiz：行情)作为其突触后合作伙伴。AIY用于区分潜力的分子机制靶点和形式的功能神经元电路尚不清楚。在这里，我建议描述一下如何通过研究突触在线虫大脑复杂环境中调节突触发生在趋热性神经回路中形成。AIY突触上的可视正向遗传屏幕已经产生多个突触模式异常的突变体。我将通过以下方式鉴定AIY突触特异性分子描述这些变种人的特征。对一类突变体的初步鉴定表明，免疫球蛋白超家族蛋白UNC-40/DCC以细胞自主的方式指导AIY突触发生。在UNC-40中突变体AIY显示正常的轴突轨迹和异常的突触前位置。UNC-40本地化到AIY 野生型动物的突触前部位。此外，UNC-40的错误定位导致异位突触前在错位的UNC-40位置的终端形成。进一步的实验将确定这种机制。 UNC-40通过它来指导AIY中突触靶点的选择。具有相似AIY的突变体的未来特征作为UNC-40的表型将决定导致正确AIY的分子信号通路突触发生。我们的工作共同承诺让我们深入了解线虫大脑中正确的突触发生。突触发生的改变可能导致许多神经发育障碍和人类疾病，如精神分裂症和自闭症。理解正确的突触发生应该有助于我们深入了解神经回路是如何构建的。以及这些回路的正确形成如何影响行为。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Functional organization of a neural network for aversive olfactory learning in Caenorhabditis elegans.

DOI：
10.1016/j.neuron.2010.11.025
发表时间：
2010-12-22
期刊：
NEURON
影响因子：
16.2
作者：
Ha, Heon-ick;Hendricks, Michael;Shen, Yu;Gabel, Christopher V.;Fang-Yen, Christopher;Qin, Yuqi;Colon-Ramos, Daniel;Shen, Kang;Samuel, Aravinthan D. T.;Zhang, Yun
通讯作者：
Zhang, Yun

Synapse formation in developing neural circuits.