Student Theses and Dissertations


Raphael Cohn

Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Ruta Laboratory


To survive in a complex and dynamic environment, animals must adapt their behavior based on their current needs and prior experiences. This flexibility is often mediated by neuromodulation within neural circuits that link sensory representations to alternative behavioral responses depending on contextual cues and learned associations. In Drosophila, the mushroom body is a prominent neural structure essential for olfactory learning. Dopaminergic neurons convey salient information about reward and punishment to the mushroom body in order to adjust synaptic connectivity between Kenyon cells, the neurons representing olfactory stimuli, and the mushroom body output neurons that ultimately influence behavior. However, we still lack a mechanistic understanding of how the dopaminergic neurons represent the moment-tomoment experience of a fly and drive changes in this sensory-to-motor transformation. Furthermore, very little is known about how the output neuron pathways lead to the execution of appropriate odor-related behaviors. We took advantage of the mushroom body’s modular circuit organization to investigate how the dopaminergic neuron population encodes different contextual cues. In vivo functional imaging of the dopaminergic neurons reveals that they represent both external reinforcement stimuli, like sugar rewards or punitive electric shock, as well as the fly’s motor state, through coordinated and partially antagonistic activity patterns across the population. This multiplexing of motor and reward signals by the dopaminergic neurons parallels the dual roles of dopaminergic inputs to the vertebrate basal ganglia, thus demonstrating a conserved link between these distantly related neural circuits. We proceed to demonstrate that this dopaminergic signal in the mushroom body modifies neurotransmission with synaptic specificity and temporal precision to coordinately regulate the propagation of sensory signals through the output neurons. To explore how these output pathways ultimately influence olfactory navigation we have developed a closed loop olfactory paradigm in which we can monitor and manipulate the mushroom body output neurons as a fly navigates in a virtual olfactory environment. We have begun to probe the mushroom body circuitry in the context of olfactory navigation. These preliminary investigations have led to the identification of putative pathways for linking mushroom body output with the circuits that implement odor-tracking behavior and the characterization of the complex sensorimotor representations in the dopaminergic network. Our work reveals that the Drosophila dopaminergic system modulates mushroom body output at both acute and enduring timescales to guide immediate behaviors and learned responses.


A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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