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

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.