From genes to behavior: genetic dissection of visual circuitry using Drosophila melanogaster

• Applicant: Professor Dr. Mathias Wernet
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 269962750

The goal of this proposal is to elucidate how genes control visual behaviors. We focus on identifying those neural circuits underlying one specific visual response. This will be followed by a detailed characterization of the development and function of identified cell types within these neural circuits. Our approach will lead to a better understanding of how basic computations are performed by neural circuits with respect to one specific visual behavior. We use the fruitfly Drosophila melanogaster as a powerful molecular genetic model organism. Like many insects, as well as some vertebrates, Drosophila can detect the e-vector orientation of incident light, commonly known as polarization. In nature, polarized light is created through athmospheric scattering, as well as through reflection from shiny surfaces, like water. Both stimuli have proven important for many animals, by serving as a stimulus improving their navigational skills, or by guiding them towards sites of reproduction. We are combining three experimental aims: First, we will genetically identify those cell types crucial for the behavioral response to linearly polarized light (Aim I). A combination of behavioral assays and genetic screens will be used to identify those neurons computing critical steps in polarization vision. From this collection of cellular units, the polarization vision circuit will be assembled, using molecular genetic tools pioneered in Drosophila. The genetic lines targeting these cell types of interested will serve as a basis for the functional characterization of these circuit elements (see below). Secondly, we will Visualize the electrical activity of identified circuit elements in vivo (Aim II). Genetically inducible, fluorescent Calcium sensors will be used to visualize the functional response properties of identified cell types to polarized light, in the behaving animal. A combination with in vivo circuit breaking tools (inactivation, over-activation of cell types) will then reveal the cells computational roles within the circuit. In different international collaborations, these studies will be extended towards using electrophysiology. Thridly, we will investigate the transcriptional profiles of identified cell types in the visual circuit (Aim III). To achieve this goal we will use state-of-the-art techniques like damID and RNAseq. These studies will reveal the transcriptional landscape shaping the functional properties of cell types within the polarization vision circuit, as well as the transcription factor code defining their identities. This project will be performed in close collaboration with Prof. Claude DESPLAN, at the Department. of Biology, at New York University. In conclusion, we aim for a cellular description of how neural circuits drive specific visual behaviors. Our findings will provide synergistic insight for ongoing studies on motion vision and color discrimination.

• DFG Programme: Research Grants
• International Connection: USA
• Cooperation Partner: Professor Claude Desplan, Ph.D.