Role of synaptotagmins and neurexin ligands in homeostatic synaptic plasticity

突触结合蛋白和神经毒素配体在稳态突触可塑性中的作用

• 批准号: 8854550
• 负责人: Lu Chen
• 金额: $ 36.73万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8854550
• 关键词: Address; Adult; Affect; Animals; Arts; Behavior; Behavioral; Cell Adhesion Molecules; Collaborations; Complement; Dependence; Excitatory Synapse; Exocytosis; Genetic; Goals; Hippocampus (Brain); Inhibitory Synapse; Investigation; Knock-out; Knockout Mice; Learning; Ligands; Mediating; Memory; Mental disorders; Molecular; Mus; Neurosciences; Organism; Pathway interactions; Plastics; Principal Investigator; Process; Proteins; Pyramidal Cells; Rest; Role; SNAP receptor; Signal Pathway; Signal Transduction; Synapses; Synaptic Vesicles; Synaptic plasticity; Tretinoin; Virus; Work; autism spectrum disorder; base; behavioral study; driving behavior; in vivo; insight; interest; learned behavior; memory encoding; nervous system disorder; neural circuit; novel; postsynaptic; receptor; recombinase; research study; small hairpin RNA; synaptogenesis; synaptotagmin; tool; trafficking

Center PI: Malenka, Robert, Principal Investigator: Chen, Lu/Südhof, Thomas (Project 3) Summary A long-standing question in the field of neuroscience is how plastic changes at synapses in a circuit enable learning, encode memory, and drive behavior. Compared to the progress made in relating Hebbian plasticity to animal learning, little is known about the behavioral significance of homeostatic synaptic plasticity. Based on the newly discovered signaling pathway involved in homeostatic synaptic plasticity – the synaptic retinoic acid pathway, and building on the progress made in the past years, this study aims to deepen our understanding of homeostatic synaptic plasticity by further exploring the involvement of postsynaptic exocytosis machineries and trans-synaptic adhesion molecules in homeostatic synaptic plasticity. Moreover, taking advantage of the known molecular components uniquely involved in the homeostatic synaptic plasticity, the study will probe in vivo functional significance of homeostatic plasticity by applying state-of-art genetic tools in animal behavioral studies. Through close collaboration with other projects of the Center, this project hopes to provide conceptual advancement to our understanding of homeostatic synaptic plasticity and retinoic acid signaling. Relevance The candidate molecules investigated in this project have been implicated in Autism spectrum disorders. Dissecting their involvement in homeostatic synaptic plasticity and RA signaling and examining the functional impact on animal learning when homeostatic plasticity is compromised will further our understanding of circuit maladaptation underpinning mental illnesses. PHS 398/2590 (Rev. 11/07) Page 1 Summary

中心PI：马伦卡，罗伯特，首席研究员：陈，卢/苏德霍夫，托马斯（项目3） 概括 神经科学领域的一个长期存在的问题是，电路中的突触时塑料变化如何启用 学习，编码内存和驱动行为。与将Hebbian可塑性与 动物学习，对稳态突触可塑性的行为意义知之甚少。基于 与稳态合成可塑性有关的新发现的信号通路 - 合成视黄酸 这项研究旨在加深我们对 通过进一步探索突触后胞吞机器和 稳态合成可塑性中的反式突触粘合剂分子。而且，利用已知的 该研究将在体内进行探测 通过在动物行为中应用最先进的遗传工具的稳态可塑性的功能意义 研究。通过与中心其他项目的密切合作，该项目希望提供概念 我们对体内稳态可塑性和视黄酸信号传导的理解发展。 关联 该项目中研究的候选分子已在自闭症谱系障碍中隐含。 解剖他们参与体内稳态可塑性和RA信号传导并检查功能 损害稳态可塑性时对动物学习的影响将进一步了解我们对电路的理解 疾病的基础是精神疾病。 PHS 398/2590（Rev. 11/07）第1页摘要