Description
- Abstract:
- The flexibility of circuits is integral for learning and adaptive behavior. Substances of abuse corrupt circuits and generate repetitive behavioral loops. The mechanisms underlying how substances of abuse co-opt neural circuitry to generate long-lasting memories and maladaptive behavioral patterns is still poorly understood. Drosophila melanogaster provide an opportunity to investigate the plasticity occurring within neural circuits responsive to reward after exposure to substances of abuse like alcohol with high resolution. I initially map out the circuitry underlying reward response within Drosophila, highlighting the diversity of signaling molecules and propose a model of how they work synchronously to generate appropriate behavioral responses. Subsequently, I utilize in vivo 2-photon calcium imaging of dopaminergic circuits within Drosophila to investigate how repeated exposure to alcohol in the presence of cues influences neural activity. Our study finds that alcohol in the presence of a cue potentiates dopaminergic circuits and downstream cue-encoding neurons in manners not observed during presentation of alcohol alone, or with arbitrary associations. Alongside this, we also address how the molecular composition of cue-encoding neurons is changing after formation of alcohol-cue memories. Using RNA-sequencing, we were able to characterize differential transcriptional programs occurring with memory formation. These changes were mainly at the RNA level and required spliceosome machinery for proper encoding behavioral experiences. Building from this, I sought to understand how alcohol-induced splicing of Drosophila D2-like receptor influences reward response. Using a CRISPR-Ca9 generated Drosophila mutants in conjunction with multiple behavioral assays, I found that an isoform expressed after formation of alcohol-associative memory increases preference for alcohol and sucrose compared to flies that have an isoform expressed before memory formation. Finally, I discuss the how my work contributes to our understanding of how alcohol-associative memories influences plasticity at both the circuit and molecular level, and how my work serves as a framework to understand how dynamic splicing is influencing behavior.
- Notes:
- Thesis (Ph. D.)--Brown University, 2025
Citation
Brown, Tariq Maxzavier,
"Alcohol-Induced Plasticity within Dopaminergic Memory Circuits in Drosophila"
(2025).
Neuroscience Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:ywxejmgv/
