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The Molecular Basis of Olfactory Driven Behaviors in Drosophila melanogaster

Abstract

The organization and functionality of the fly olfactory system is orchestrated by complex molecular events, and the Drosophila model offers the tools necessary to understand the genetic basis of these events. This work aims to further characterize the molecular basis of olfactory driven behaviors in Drosophila. I will explore several topics to this end: The reliance of innate chemotaxis behavior on single receptor genes, the regulation of receptor gene choice, and a novel molecular mechanism required for olfactory learning and memory.

In Part I, I demonstrate that loss of single receptor genes can disrupt innate avoidance behaviors. First, I identify a novel aversive channel in the larvae governed by Or7a. Or7a mutants lose the ability to detect and respond to low concentrations of the food odorant E-(2)-hexenal. Secondly, I show that loss of Gr63a’s co-receptor Gr21a completely disrupts neuronal and behavioral response to carbon dioxide in adult flies. In both cases, I employed the emergent CRISPR/Cas9 system to create targeted knock-out mutations in Drosophila.

In Part II, I show that members of the chromatin modifying complex MMB/dREAM regulate expression of carbon dioxide receptors Gr63a and Gr21a. Using RNA-seq to analyze antennal transcriptomes, I observe differential expression of several other olfactory receptor genes in dREAM complex mutants, suggesting a broader role in olfactory receptor regulation for this multi-protein complex.

In Part III, I find that HDAC6, a largely cytoplasmic protein, is required for retention of olfactory memory in both larvae and adults. HDAC6 mutants also exhibit defects in synaptic plasticity at the larval neuromuscular junction, suggesting an interesting connection between molecular events at active zones and behavioral plasticity.

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