Investigating Octopaminergic Neural Circuitry in Olfactory Appetitive Memory

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DESCRIPTION (provided by applicant): RELEVANCE OF RESEARCH TO PUBLIC HEALTH A vital objective of neural science is to identify the neural circuits that encode memory and guide behavior. Drosophila is an ideal model organism to study the neural basis of memory because they can be taught to pair a conditioned stimulus (odor) with a salient unconditioned stimulus (sucrose reward) and assayed for the learned association. Furthermore, the genetics and evolving technologies available in Drosophila allow for precise temporal and spatial manipulation of neural circuits. This proposal focuses on the monoamine, octopamine, the insect functional equivalent of mammalian noradrenaline and its specific role in appetitive memory. The primary goal is to demonstrate whether octopaminergic neurons signal the instructive unconditioned stimulus and are required at the time of CS-US association, or if they are instead involved in the animal's hunger drive leading up to the CS-US association. In addition, this proposal seeks to identify the memory-relevant octopamine receptors and their location of action in the fly brain. There are several human disease-states, including affective disorders and addiction, where patients lose appetitive control leading to compulsive behavior. The research proposed in this grant aims to investigate how the brain systems encoding appetitive memory integrate the neural networks conveying the conditioned and unconditioned stimuli and will help understand the mechanistic properties behind human appetitive afflictions.