How do neuropeptides shape sensory processing in Drosophila?

Neuropeptides, potent modulators governing diverse physiological and behavioral realms, intersect with all functions and areas of the brain, including sensory systems. Their modulation can have profound effects on perception and subsequent behavior. In Drosophila melanogaster, we have a detailed understanding of the neurons and their computations that underlie the visual system. However, our understanding is built almost primarily on the study of neuromodulators such as neurotransmitters. Despite mounting evidence of their potential roles, have almost no information regarding how neuropeptides mechanistically modulate neural systems. In the work included in this dissertation, I deployed optogenetics, two-photon imaging of neural calcium signaling, and chemical and genetic perturbations of a peptidergic system to uncover evidence of the integral role of neuropeptides in visual processing. Chapter 1 of the thesis is a review of neuropeptides and their potential impact on sensory systems, culminating on an explanation of the Drosophila visual system. It is here that I discuss the known aspects of neuropeptidergic signaling, the functional role of neuropeptides broadly in within the brain and body, and the evidence of neuropeptidergic modulation of sensory systems. The following chapter focuses on the major project of my doctoral training. In it, I detail the influence of a particular neuropeptide Allatostatin A (AstA) and the ways that it impacts the Drosophila visual system (Chapter 2). This system, laid out with retinotopic precision and performing a myriad of computations on incoming visual stimuli, has primarily been understood as one of synaptic signaling. I have found that AstA is released in a very small number of neurons in the visual system, while many neurons express its receptors. Many of these neurons have known roles in visual processing, and Mi1 in particular is a well-studied neuron that contributes to the processing of light and is integral to the ability of the fly to see motion. Through optogenetic activation of AstA neurons, perfusion of AstA, and genetic manipulations of the AstA receptor in Mi1, I have determined how the presence of AstA changes Mi1's stereotyped response to light and how the peptide helps shape the neuron's canonical response. This represents the first evidence of a fundamental role of neuropeptides in visual processing. This chapter also presents a more harmonized understanding of how neuropeptides interface with sensory systems to alter their responses to stimuli. The work underscores the importance of examining neural systems through a multi-faceted lens, considering neuropeptidergic signaling as well as typical neurotransmitter modulation to neural circuits. Chapter 3 focusses on the behavioral and evolutionary differences associated with fruit fly species. Various species and strains of fruit flies were recorded as they walked freely in a large arena, and a comparison of the features of their behavior with the features of their genetics led to a unique understanding of the temporal dynamics of evolutionary changes across clades. The behavioral data I collected for this study was similarly utilized in Chapter 4 of my thesis. In that work, my coauthors and I explored how specific neurons in the visual system of flies are modulated by self-motion, and that this modulation allows for a more reliable feature detection during fly locomotion. The stimuli showed to the flies were constructed using trajectories from the same behavioral arena to better simulate the visual statistics a fly would encounter during the normal course of its locomotor behavior. My dissertation culminates with a summary of the findings, their situation in the field of visual neuroscience and neuropeptide research, and suggestions for future experiments and ways for the field to move forward as we strive to understand the role of neuropeptides in sensory processing (Chapter 5).

Keywords: Medicine.
Advisor: Clandinin Thomas
Druckmann Shaul
Giocomo Lisa
Parker Karen