Role of spontaneous activity and electrical coupling in coordinating the development of direction-selective neurons in Drosophila melanogaster

• Applicant: Dr. Camille Guillermin, Ph.D.
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Developmental Neurobiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 579350263

Brain development establishes the foundation for neurons to acquire the properties required to transform sensory information into meaningful computations. An intensively studied neural computation is the establishment of direction selectivity (DS), a hallmark of motion detection. In Drosophila, the first DS cells are the T4 and T5 neurons (T4/T5), whose dendritic architecture and synaptic connectivity support local motion computation. At the population level, T4/T5 neurons then encode global optic flow patterns. While the adult circuit is well-characterized, how T4/T5 acquire their functional morphology, connectivity, and tuning during development remains largely unknown. Spontaneous neuronal activity during early development is a key driver of circuit assembly. In vertebrates, retinal waves promote neuronal survival, synaptogenesis, and the organization of topographic maps, before any external sensory experience. Electrical coupling via gap junctions is essential for the propagation of retinal waves, and their disruption impairs spontaneous firing patterns and circuit assembly. Analogously, recent works revealed that the developing Drosophila visual system exhibits spontaneous activity, called patterned stimulus-independent neuronal activity (PSINA), during pupal synaptogenesis. While this is happening at a time when T4/T5 neurons undergo dendrite growth and synaptogenesis, it is not known if PSINA tunes function. I will test the hypothesis that PSINA, potentially mediated by innexin-dependent electrical coupling, acts as an instructive signal that coordinates T4/T5 survival, connectivity, and tuning, and thus shapes adult function in local or global motion computation. Preliminary results support this view: innexin expression peaks during synaptogenesis, apoptotic events occur within the T4/T5 lineage, and genetic disruption of PSINA (in trp-γ mutants) leads to impaired T4/T5 directional tuning. Specifically, I will first use developmental live imaging to determine the role of innexin-mediated electrical coupling in coordinating PSINA.I will then use immunohistochemistry and high-resolution imaging to assess how PSINA influences T4/T5 survival, morphology, and synaptic wiring. Third, I will use in vivo two-photon imaging and genetic manipulations to evaluate whether PSINA affects functional DS tuning at both single-cell (local DS) and population levels (encoding of optic flow). This research will provide a comprehensive understanding of how early spontaneous activity patterns shape the structural and functional maturation of DS circuits. By uncovering how intrinsic, coordinated activity during development sculpts precise neural circuits, this work can reveal fundamental principles governing how brains transform transient developmental events into reliable sensory computations, offering insights of how complex neural networks are built and refined.

• DFG Programme: Position