UC Irvine

The broader theme of this dissertation is concerned with the molecular mechanismsemployed by neurons to regenerate dendrites after injury, with a special emphasis on dendrite injury detection. Much of the work provides evidence for a fundamental, yet necessary, question: Does dendrite injury trigger calcium influx and, if so, how necessary is this early calcium influx for repair? To answer this, I used Drosophila dendritic arborization neurons of the larval peripheral nervous system as a model. Injuries were performed using precise two-photon laser-mediated removal of dendrites in live, intact larvae. Elevations in calcium were measured using the most advanced version of the genetically encoded calcium indicator GCaMP7f and morphological regeneration was assessed using membrane-bound fluorophores. The findings indicate that dendrite injury-induced elevations in calcium may be cell type- and neurite type-specific. Importantly, shunting injury-induced calcium influx resulted in less, but not abolished, regeneration, suggesting that this early calcium plays a supportive role in dendrite regeneration. Mechanistically, I provided evidence for the positive role of L-type VGCCs, IP3 signaling, and PKD activity on dendrite regeneration. In addition to my research endeavors, this thesis also describes my experience completing a graduate research internship with Eli Lilly and Company in Boston, MA. I then reflect on how that opportunity made me a better scientist, and briefly discuss the literature on graduate student internships. Lastly, I detail the results of some final projects regarding the roles of histone deacetylases, protein kinase D, and the neuronal cytoskeleton, in addition to the use of hippocampal neuron culture to study dendrite regeneration in a system that provides unique characteristics distinct from fly sensory neurons.