Dissertations, Theses, and Capstone Projects

Date of Degree

2-2023

Document Type

Thesis

Degree Name

M.S.

Program

Cognitive Neuroscience

Advisor

Jeff Beeler

Subject Categories

Systems Neuroscience

Keywords

sensitization, fiber photometry, dopamine, acetylcholine, cocaine, amphetamine

Abstract

Drug-induced behavioral sensitization describes the phenomenon that behavioral response to a drug of abuse is getting stronger if the same psychostimulant is delivered multiple times which is much more pronounced if done in the same environmental context. A proposed neural basis is the formation of an association between contextual cues and the rewarding drug which is mediated by dopamine. Dopamine operates at different timescales and to fully understand dopamine sensitization, it is necessary to investigate dopamine release at slow (tens of minutes) but also faster (sub-second) timescales. But creating a holistic view has been difficult due to a lack of technology that can measure dopamine across various temporal resolutions. We develop an analysis pipeline to expand fiber photometry to measure tonic dopamine activity. We use genetically encoded neurotransmitter indicators to measure extracellular dopamine and acetylcholine activity in the nucleus accumbens of mice. We show that the method is precise enough to measure dopamine sensitization in response to repeated cocaine and amphetamine injections. We then further characterize how dopamine dynamics change in response to psychostimulants. We see that drug-evoked dopamine rises and decays faster in sensitized mice compared to the first injection and that there are more small but less big transients which leads to a smaller fluctuation at a timescale of tens of seconds. We simultaneously record striatal acetylcholine and observe that the frequency and amplitude of transients decrease during sensitization. We also investigate interaction between dopamine, acetylcholine, and movement and report that the relationship between accumbal activity and locomotion gets stronger and that dopamine and acetylcholine interact closely. In addition, we use DeepLabCut and MoSeq to densely annotate behavior. We show that MoSeq can potentially be used to replace locomotor activity with a better measurement of behavioral sensitization.

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