ABSTRACT The developing brain becomes active before it is ready to receive sensory input. Such stimulus-independent developmental activity was originally described and characterized in the visual system over three thirty years ago. Since then, the phenomenon has been observed and studied in many additional areas of the brain, including other sensory systems as well as in the thalamus and cortex. Where tested, altering developmental activity leads to disorganization of neuronal connections. While its role in instructing wiring fidelity has received significant attention, two important questions about developmental activity remain largely unaddressed: First, is the activity is coordinated across disparate brain regions? And, secondly, what is the significance of developmental activity to shaping behavior, and more specifically, how does it contribute to the maturation of a healthy nervous system? Understanding brain development is a significant scientific challenge with direct relevance to human health. Studies into the causes of neurodevelopmental disorders rightly cast a wide net, covering progressive stages of neural development from proliferation to morphogenesis to synaptogenesis. Notably, developmental activity— as an evolutionarily conserved process—remains a blind spot, mostly due to the challenges of working with the mammalian model: both in utero development and the daunting size and complexity, make the requisite exploratory studies prohibitively costly. The fruit fly brain also has developmental activity comparable to that seen in mammals. Patterned, Stimulus- Independent Neural Activity (PSINA, ‘see-nah’) engages the whole brain in highly structured and stereotyped activity, providing neurons their first opportunity to communicate across previously inaccessible spatiotemporal scales. The fly, with its approachably complex brain and an ever-expanding molecular-genetic toolkit, is at the forefront of cellular, systems, and behavioral neuroscience research. The discovery of PSINA introduced this powerful fly model to complement mammalian studies into developmental activity. Recently, our lab reported that a population of ~2,000 neurons, genetically defined by their expression of the cation channel Trpγ, is critical to coordinating PSINA across the brain. We know that a much smaller subset of this population is directly involved in PSINA. In my first Aim, I will use a recently developed molecular-genetic approach to functionally fractionate Trpγ+ population down to individual cells. In the process, I will learn how the circuitry of PSINA is organized to produce its distinct spatiotemporal structure. Further insights into the biology of PSINA will come from my second Aim, where I will ask how a neuropeptide signaling pathway acts through specific neurons to shape the activity. With the successful completion of this project, we will gain the experimental control to explore how critical brain functions, from sensory processing to sleep and ...