GSBS Dissertations and Theses

Publication Date


Document Type

Doctoral Dissertation

Academic Program



Department of Neurobiology; Waddell Lab

First Thesis Advisor

Scott Waddell


Drosophila, reward, conditioning


Dissertations, UMMS; Reward; Reinforcement (Psychology); Neural Pathways; Drosophila melanogaster; Octopamine; Dopamine; Signal Transduction


Evaluating our environment by deciding what is beneficial or harmful, pleasant or punishing is a part of our daily lives. Seeking pleasure and avoiding pain is a common trait all mobile organisms exhibit and understanding how rewarding stimuli are represented in the brain remains a major goal of neuroscience. Studying reward learning in the fruit fly, Drosophila melanogaster has enabled us to better understand the complex neural circuit mechanisms involved in reward processing in the brain. By conditioning flies with sugars of differing nutritional properties, we determined that flies trained with sweet but non-nutritive sugars formed robust short-term memory (STM), but not long-term memory (LTM). However, flies conditioned with a sweet and nutritious sugar or a sweet non-nutritious sugar supplemented with a tasteless nutritious compound, formed robust 24 hour LTM. These findings led us to propose a model of parallel reinforcement pathways for appetitive olfactory conditioning in the fly, in which both sweet taste and nutrient value contribute to appetitive long-term memory. We followed this line of research by examining the neural circuitry in the fly brain that represents these parallel reward pathways. We found that the biogenic amine octopamine (OA) only represents the reinforcing effects of sweet taste. Stimulation of OA neurons could replace sugar in olfactory conditioning to form appetitive STM. Surprisingly, implanting memory with OA was dependent on dopamine (DA) signaling, which although being long associated with reward in mammals, was previously linked with punishment in flies. We found that OA-reinforced memory functions through the α-adrenergic OAMB receptor in a novel subset of rewarding DA neurons that innervate the mushroom body (MB). The rewarding population of DA neurons is required for sweet and nutrient reinforced memory suggesting they may integrate both signals to drive appetitive LTM formation. In addition, OA implanted memory requires concurrent modulation of negatively reinforcing DA neurons through the β-adrenergic OCTβ2R receptor. These data provide a new layered reward model in Drosophila in which OA modulates distinct populations of both positive and negative coding DA neurons. Therefore, the reinforcement system in flies is more similar to that of mammals than previously thought.



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