RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS

神经科学中最基本的问题之一是神经元的灵活性是如何发生的，以及为什么神经元的变化能力在有机体的生命过程中通常会减弱。在年轻的生物体中，神经系统是高度可塑性的；神经细胞可以改变它们的形状和功能。在较老的神经系统中，大规模重组是不寻常的。某些被称为神经营养因子的生长因子被认为对许多生物的早期神经元灵活性起到了作用，从苍蝇到人类。本研究的目的是了解一类神经营养生长因子家族是否影响发育中和成年蟋蟀神经元的发育、维持和可塑性。板球特别值得研究，因为它在负责听力的电路中展示了不同寻常的神经元灵活性。由于这些生长因子在各种生物体中都很保守，从这些板球实验中学到的东西将普遍适用于其他生物体的回路。这项工作的更广泛的科学影响将是它对更深入地理解神经系统发育和可塑性的机制的贡献。这项工作还将对鲍登学院和缅因州的教育产生重要影响。本科生将积极参与拟议的科学研究，并将特别努力从代表不足的群体中发现、支持和留住学生。此外，PI和她的学生将参加当地小学和Wabanaki中学生的年度STEM外展活动，扩大该基金的社会影响。神经营养素已知调节哺乳动物发育和成熟神经元的生存、分化和可塑性。也有证据表明，神经营养素-Trk和Semaphorin-Plexin信号之间存在串扰，这两个信号塑造了哺乳动物的树突形态。昆虫神经系统缺乏神经营养因子的假说正受到果蝇Spaetzle(SPZ)和Toll信号通路的营养样功能的发现的挑战。然而，需要更多的证据来支持昆虫中SPZ-Toll功能类似于典型的神经营养信号的假设。据估计，蟋蟀与果蝇的进化时间相差1.3亿年。这是一个引人注目的模型，用于探索神经营养信号，因为在成人感觉器官丧失后，存在不寻常的结构可塑性。PI和她的学生将检验SPZ-Toll信号影响板球中枢神经系统的发育和维持的假设。此外，他们将探索这种信号是否在去传入诱导的板球可塑性中发挥作用，并将启动一项关于SPZ-Toll信号是否与Semaphorin信号交叉的调查。DsRNA将被用来单独或联合操纵SPZ、Toll、Sema或Plexin候选分子的水平，并将评估和量化由此导致的发育或成年神经元形态的变化。假设神经元可塑性的策略在进化上是保守的，从使用双斑革兰氏菌的这些实验中学到的东西将适用于各种其他生物体的发育和成体回路。该项目由神经系统集群的组织计划和既定的激励竞争研究计划(EPSCoR)共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

One of the most fundamental questions in neuroscience is how neuronal flexibility occurs and why the capacity for neuronal change generally diminishes over the course of an organism’s life. In young organisms, nervous systems are highly plastic; neural cells can change their shape and their function. In older nervous systems, large-scale reorganizations are unusual. Certain growth factors, known as neurotrophins, are thought to contribute to this early neuronal flexibility in many organisms, from flies to humans. The goal of this study is to understand whether a family of neurotrophic-like growth factors influences the development, maintenance, and plasticity of neurons in developing and adult crickets. The cricket is particularly compelling to study since it demonstrates an unusual level of neuronal flexibility in circuits responsible for hearing. Because these growth factors are well-conserved in a variety of organisms, what is learned from these cricket experiments will be generally applicable to circuits in other organisms. The broader scientific impact of the work will be its contribution to a deeper understanding of the mechanisms of nervous system development and plasticity. This work will also have important educational impacts both at Bowdoin College and within Maine. Undergraduates will be active participants in the proposed scientific research, and a special effort will be made to identify, support, and retain students from underrepresented groups. In addition, the PI and her students will participate in annual STEM outreach activities at local elementary schools and with Wabanaki middle school students, widening the societal impact of the funding.Neurotrophins are known to mediate the survival, differentiation, and plasticity of developing and mature neurons in mammals. There is also evidence for cross-talk between neurotrophin-Trk and Semaphorin-Plexin signaling, which shapes mammalian dendritic morphology. The assumption that neurotrophins are absent from insect nervous systems is being challenged by the discovery of trophic-like functionality of the Spaetzle (Spz) and Toll signaling pathway in Drosophila. However, additional evidence is necessary to support the hypothesis that Spz-Toll function in insects is akin to canonical neurotrophic signaling. The cricket, Gryllus bimaculatus, is separated from Drosophila by an estimated 130 million years of evolution. It is a compelling model in which to explore neurotrophic signaling due to the presence of the unusual structural plasticity seen in the adult after sensory organ loss. The PI and her students will test the hypothesis that Spz-Toll signaling influences the development and maintenance of the cricket CNS. Further, they will explore whether this signaling plays a causative role in the deafferentation-induced plasticity present in the cricket and will initiate an investigation into whether Spz-Toll signaling intersects with Semaphorin signaling. DsRNA will be used to manipulate levels of Spz, Toll, Sema or Plexin candidates individually or in combination, and resulting changes in developmental or adult neuronal morphology will be assessed and quantified. Given presumed evolutionary conservation of strategies for neuronal plasticity, what is learned from these experiments using G. bimaculatus will be applicable to developing and adult circuits in a wide variety of other organisms. This project is jointly funded by the Neural Systems Cluster's Organization program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.