Molecular coordination of adhesion molecules in foraging behaviors and circuits

项目概要/摘要： 我们用的是小线虫C。作为一种实验上易于处理的模型， 研究保守基因在神经元、回路和行为可塑性中的分子作用。我们 目的是在其他生物体不可能的水平和范围上研究行为的产生， 包括跨多个行为和电路的许多基因的并行分析。这包括 了解基因的贡献和相互作用的目标，甚至是单一的异构体， 基因，行为。通过关注与以下疾病相关的基因的保守直系同源物， 神经发育和神经精神障碍，以行为变化为特征，我们 希望扩大我们对基因在行为中作用的理解。我们的分子解剖 在行为回路之间和跨行为回路的单个神经元中的基因功能导致了对 经验依赖性神经元的新分子机制和遗传相互作用 可塑性和行为可塑性。在这里，我们集中在突触细胞粘附分子（sCAMs） 基因，包括neurexins和neuroligins，这是非常复杂和冗余的基因 脊椎动物的家族脊椎动物神经元、回路和sCAM的复杂性和多样性 基因已经阻止了在遗传、分子、电路和行为上的同时分析。 我们希望实现的解决方案。我们建议使用C。作为一个易于处理的实验 系统同时研究分子和电路机制的许多 突触粘附基因在多种行为中的作用我们未来几年的研究计划是 为了扩大我们正在深入研究的sCAM基因的列表，以获得更细致和完整的 行为中sCAM基因的分子协调图。使用一套现代遗传学 和神经科学技术，我们计划1）确定涉及多个sCAM基因网络 觅食行为，2）定义细胞，亚细胞，分子和时间的要求， 每个鉴定的sCAM基因，和3）表征每个sCAM基因对结构的影响 和觅食回路的功能连接性，都是在单神经元分辨率下。我们自上而下 这种方法在很大程度上依赖于使用行为作为基因和电路功能的读出器， 这将为研究行为的遗传和分子基础提供一个独特的窗口。成功 我们工作的完成将使我们对神经元回路的原理有更深的理解 形成，功能和行为输出，涉及基础和疾病重点 学科C.线虫不仅是一个独特的易于处理的实验模型， 我们提出的实验，但也提供了一个包容性的实验系统，以培训/导师 本科生，研究生，和博士后在所有层次的经验。

Project Summary/Abstract: We are using the small nematode C. elegans as an experimentally tractable model to study the molecular roles of conserved genes in neuronal, circuit, and behavioral plasticity. We aim to study the generation of behavior at a level and scope not possible in other organisms, including parallel analysis of many genes across multiple behaviors and circuits. This includes the goal of understanding the contribution and interactions of genes, and even single isoforms of genes, in behavior. By focusing on conserved orthologs of genes associated with neurodevelopmental and neuropsychiatric disorders, characterized by changes in behavior, we hope to expand our understanding of the role of genes in behavior. Our molecular dissection of gene function in single neurons between and across behavioral circuits has led to identification of novel molecular mechanisms and genetic interactions in experience-dependent neuronal plasticity and behavioral plasticity. Here we focus on synaptic cell adhesion molecule (sCAMs) genes, including neurexins and neuroligins, which are extremely complex and redundant gene families in vertebrates. The complexity and diversity of vertebrate neurons, circuits, and sCAM genes have prevented simultaneous analysis at the genetic, molecular, circuit, and behavioral resolution we hope to achieve. We propose to use C. elegans as a tractable experimental system to simultaneously investigate the molecular and circuit mechanisms of many synaptic adhesion genes in multiple behaviors. Our research plans over the coming years are to expand the list of sCAM genes we are studying in depth to gain a more nuanced and complete picture of the molecular coordination of sCAM genes in behavior. Using a suite of modern genetic and neuroscience techniques we plan to 1) Identify networks of sCAM genes involved in multiple foraging behaviors, 2) Define the cellular, subcellular, molecular, and temporal requirements of each identified sCAM gene, and 3) Characterize the impact of each sCAM gene on the structure and functional connectivity of a foraging circuit, all at single neuron resolution. Our top-down approach relies heavily on using behavior as a readout of gene and circuit function, with the hope this will provide a unique window into the genetic and molecular basis of behavior. Successful completion of our work will result in a deeper understanding of the principles of neuronal circuit formation, function, and behavioral output with implications across basic and disease-focused disciplines. C. elegans are not only a uniquely tractable experimental model for the resolution of experiments we propose, but also provide an inclusive experimental system to train/mentor undergraduates, graduate students, and postdocs at all levels of experience.