Cell-intrinsic and circuit mechanisms that shape visual processing in Drosophila

Vision is critical for the survival of many organisms and involves both detecting environmental stimuli and determining its meaning. That is, visual systems are responsible for not only detecting the spatial and temporal distribution of light, but also transforming raw visual inputs into relevant behavioral responses. While the molecular mechanisms of phototransduction, as well as the algorithms underlying downstream visual computations, have been well-studied (Katz and Minke, 2018; Currier et al., 2023), the neurobiological mechanisms implementing these computations remain poorly understood. How do the cell-intrinsic properties of different neural cell types, as well as their synaptic connections within microcircuits, shape visual processing? The Drosophila visual system is a highly tractable model for the type of neural circuit dissection necessary to address these questions. The rich history of genetic studies on visually-dependent behavior, along with more recent efforts to develop comprehensive genetic tools, together enable experiments targeting questions from both neurobiological and computational angles. Interneurons in the early visual system are genetically accessible, and their synaptic wiring diagram and gene expression profiles are well-characterized (Pfeiffer et al., 2008; Jenett et al., 2012; Dionne et al., 2018; Rivera-Alba et al., 2011; Takemura et al., 2017; Shinomiya et al., 2019; Kurmangaliyev et al., 2020; Davis et al., 2020; ̈Ozel et al., 2021; Konstantinides et al., 2022). Many studies have measured the response properties of these interneurons and their impact on visually-evoked behavior (Currier et al., 2023). Additionally, efforts to develop increasingly effective and diversified fluorescent indicators of neural activity, as well as in vivo microscopy techniques, have made it possible to acquire highly precise and nuanced physiological measurements in this system (Chen et al., 2013; Dana et al., 2016; Yang and St-Pierre, 2016; Marvin et al., 2018). This dissertation begins with a holistic introduction to visual processing in flies, from photoreceptors to behavior, spanning cellular to systems level studies. In particular, the section on the optic lobes highlights the increasing precision and scope of cellular and circuit-level questions that have become experimentally accessible within the last decade. The second chapter includes two publications to which I have contributed work demonstrating the use of novel voltage indicators in flies. Voltage indicators are a relatively new tool and have broadened the types of physiology experiments possible, especially in fly neurons, many of which are inaccessible by electrophysiology. The third chapter includes unpublished work dissecting an early visual system circuit using voltage indicators, genetic circuit perturbations, and computational modeling, demonstrating how we can connect precise cell type-specific physiological measurements to higher-level visual processing. Finally, I conclude with a discussion of the value of integrating cellular and systems level questions, and possible future directions that I hope this field will take.

Keywords: Humanities and Sciences.
Biology.
Advisor: Clandinin Thomas R. (Thomas Robert)
Chen Xiaoke
Goodman Miriam Beth
Luo Liqun