Project Summary Calcium (Ca2+) is a critical regulator of neurotransmission in both axons and dendrites of neurons. Ca2+ fluctuations during neuronal activation are usually attributed to influx through voltage gated Ca2+ channels, but in vitro evidence suggests that intracellular Ca2+ handling, particularly by the endoplasmic reticulum (ER), could shape cytosolic Ca2+ signals and therefore neurotransmission. Our preliminary data indicate that the ER in neurons of the Drosophila visual system displays Ca2+ fluctuations in response to visual stimulus in vivo. Given that altered ER Ca2+ signaling has been implicated in neurodegeneration and retinal degeneration, the objective of this work is to determine the role of ER Ca2+ signaling in Drosophila visual system neurons and determine the molecular basis of compartment specific ER Ca2+ signals in motion vision circuits. The first aim is to determine the underlying mechanisms governing compartment specific ER Ca2+ signals using in vivo 2-photon microscopy. Findings from this aim will help elucidate the functional roles of ER Ca2+ signals in axons and dendrites. The second aim is to determine the role of ER Ca2+ handling neurotransmission and in motion vision circuit function, leveraging genetic perturbations in well-defined circuits. These studies will determine if ER Ca2+ signaling shapes cytosolic Ca2+ fluctuations, linking it to circuit function and neurotransmission in the visual system. The fellowship training plan includes in vivo 2-photon imaging, Drosophila genetics, programming, and career guidance. Through training opportunities during this project, I will develop the skills to complete this work, and continue in a career in academic research.

Project Narrative Neurotransmission and proper circuit function are crucial for processing environmental stimuli. Critical to these processes are calcium fluctuations within single neurons, however intracellular contributions to these fluctuations have remained largely unexplored. This proposal aims to uncover the contribution of endoplasmic reticulum calcium handling to neurotransmission in a well-characterized Drosophila neural circuit, informing our understanding of neurotransmission and circuit function at the level of the human brain.