Linking endoplasmic reticulum calcium handling to neuronal function in vivo in the Drosophila visual system

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.