Learning and adaptation in the Drosophila olfactory system

All forms of memory rely on plasticity to correctly store information. Plasticity ensures that certain sets of cells consistently activate each other through the strengthening of certain synapses while others are weakened. This plasticity ensures that a stimulus (internally or externally generated) consistently activates the same cells to produce the same response. These plastic changes can be short-lived, lasting mere seconds, or longer-lived, lasting days, weeks, and months. To ensure accurate storage of memory tight regulation is required. Mammalian memory systems are complex, involving the integration and processing of information from a wide variety of areas. To overcome the issue of complexity memory is often studied in less complex organisms. One of the leading models for memory is the Drosophila olfactory system. In Drosophila, associative memories are formed in the Mushroom Body (MB). Over the past 30 years, work in the MB has given us massive insight into plasticity processes and the tight regulation required to ensure accurate coding. Here I aim to test the limits of this regulation and identify novel mechanisms that may ensure accurate memory storage.
First, I tested how robust activity regulation in the mushroom body is and how well it adapts to a challenge that it could face in nature,i.e, overactivity induced by pesticides in a food source. Using pesticides that increase cholinergic signaling, I hoped to identify the maximum dose a fly can ingest and still accurately encode associative memory. Furthermore, I wanted to see if the system could adapt to this disruption over time to restore functionality. In the end, I could not find a dose that significantly disrupted learning before fly death, showing that olfactory regulation is at least as robust than other vital systems.
Second, one of the major players in memory storage in mammals is nitric oxide (NO). It has also been identified as a factor in the pathogenesis of many neurological conditions. Until recently, no such role in memory had been identified in flies. I wanted to see if manipulating NO levels could disrupt memory and, if so, what effect NO had at a cellular level. Though behavioral experiments were inconclusive, I show here that mushroom body survival was reduced after high doses of the nitric oxide donor s-nitrosoglutathione (GSNO).
Finally, I looked at a more everyday challenge to the olfactory system, complex odor mixtures. I used the α′3 mushroom body output neuron (MBON), which signals novelty, to show that suppression of certain cells of the mushroom body (MB) makes the components of a mixture appear novel compared to a mixture. This suppression could provide a mechanism by which flies can learn which part of a mixture is predictive of the reward or punishment. Furthermore, I show evidence that different Kenyon cell (KC) subtypes may code mixtures differently depending on the complexity of the odor environment.