The role of gap junctions during mushroom body development and remodeling

• Applicant: Professor Dr. Oren Schuldiner
• Subject Area: Developmental Neurobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 365082554

Neuronal remodeling is a conserved strategy to refine neural circuits, but its underlying mechanisms are incompletely understood. The Drosophila mushroom body undergoes stereotypic remodeling during metamorphosis, including coordinated pruning of larval γ-Kenyon cell (γ-KC) processes, followed by regrowth to form the adult circuitry. The fine temporal transcriptional landscape of γ-KCs, which we have recently uncovered, has highlighted the dynamic expression of gap junction subunits (innexins). Despite their well-established roles in electrical coupling, the functions of gap junctions during development is less understood. In preliminary experiments, we found two innexins that are required within γ-KCs for axon pruning. For the mushroom body as a study case, we here we propose to uncover how gap junction connectivity affects brain remodeling. We will use novel strategies to map the dynamic electrical connectivity of γ-KCs during development. Furthermore, we will generate tools to follow innexin localization at subcellular resolution. Finally, we will test the effects of disrupting innexins in non-γ cells on both the electrical connectivity and pruning of γ-KCs. Together, our findings should uncover the role of gap junctions during mushroom body remodeling, thereby promoting our understanding of spatiotemporal regulation and possible synchronization of axon pruning. Our proposed experiments and tools have the potential to map a comprehensive dynamic electrical connectivity diagram - something that has not been achieved in any other experimental system, and that is crucial for the overall understanding and modeling of the mushroom body as a paradigmatic brain structure.

• DFG Programme: Research Units
• Subproject of: FOR 2705: Dissection of a Brain Circuit: Structure, Plasticity and Behavioral Function of the Drosophila mushroom body
• International Connection: Israel