Role of synaptotagmins and neurexin ligands in homeostatic synaptic plasticity

中心PI：Malenka，Robert，主要研究者：Chen，Lu/Südhof，托马斯（项目3） 总结 神经科学领域一个长期存在的问题是，神经回路中突触的可塑性变化如何使 学习、编码记忆和驱动行为。与赫布塑性理论的进展相比， 在动物学习中，对稳态突触可塑性的行为意义知之甚少。基于 新发现的参与稳态突触可塑性的信号通路--突触视黄酸 在过去几年取得的进展的基础上，这项研究旨在加深我们对 通过进一步探索突触后胞吐机制的参与， 跨突触粘附分子在稳态突触可塑性中的作用此外，利用已知的 分子成分独特地参与稳态突触可塑性，该研究将在体内探索 通过应用最新的遗传工具在动物行为中研究稳态可塑性的功能意义 问题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性的 促进我们对稳态突触可塑性和视黄酸信号传导的理解。 相关性 该项目中研究的候选分子与自闭症谱系障碍有关。 解剖它们参与稳态突触可塑性和RA信号传导，并检查它们的功能。 当稳态可塑性受损时对动物学习的影响将进一步加深我们对电路的理解 适应不良导致精神疾病 PHS 398/2590（Rev. 11/07）第1页

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