UCLA

Throughout the animal kingdom, female fertility is orchestrated by a vast number of signaling pathways. These include both direct neural regulation of reproductive tissues as well as CNS computations that indirectly affect reproductive behavior. Noradrenergic signaling in particular is known to play a critical role in regulating a variety of reproductive processes in both mammals and insects. Despite this established role, knowledge of noradrenergic mechanisms in fertility lacks detailed descriptions of the complex neural circuitry regulating required behaviors. The model organism Drosophila Melanogaster offers a unique opportunity to establish a tractable system for studying conserved principles underlying the neuromodulation of fertility with single cell resolution. In Drosophila, the ortholog of noradrenaline, octopamine (Oa), is required for egg laying as well as several other reproductive subprocesses. The goals for this dissertation were to 1) comprehensibly map octopaminergic circuitry innervating the female fly reproductive tract and 2) prove the utility of such circuitry as a model for uncovering both translationally relevant mechanisms in fertility and fundamental principles of adrenergic neuromodulation. This study provides detailed reproductive tract expression pattern analyses for all six known octopamine receptors using recently made tools for capturing genetic expression profiles with unprecedented completeness. Novel Oa receptor expression is noted among extensive networks of peripheral neurons and several other reproductive organ cell types. Stimulation of octopaminergic pathways is found to induce specific reproductive muscle cell behaviors, and an assay has been established for comparing rhythmic contractions of the lateral oviducts that are regulated by Oa. Gain of function experiments increasing activity in Oa receptor expressing neurons (OaRNs) are found to reduce egg laying, suggesting for the first time a conserved mechanism between mammals and insects where increased noradrenergic tone is associated with impaired fertility.

Novel roles for Oa receptors are also provided with an updated analysis of presynaptic Oa neurons. Neurons of the central octopaminergic cluster required for ovulation have been mapped with single cell resolution. Heterogeneity between neighboring Oa neuron projection targets pairs with heterogeneity in roles stimulating reproductive organ behavior, showing that each individual neuron in this model aminergic cluster may have a unique role in conducting egg laying. Future studies will be able to use the information in this dissertation as a basis for understanding the complexity of aminergic neuromodulation in fertility and other systems.