SEILER-DISSERTATION-2021.pdf (4.61 MB)
Download fileDopaminergic Circuits for Compulsion: The Dorsomedial Striatum in Punishment-Resistant Reward-Seeking
thesis
posted on 2021-12-01, 00:00 authored by Jillian Leigh SeilerCompulsive behavior is a defining feature of disorders such as substance use disorder and obsessive-compulsive disorder. Current evidence suggests that corticostriatal circuits control the expression of established compulsions, but little is known about the mechanisms regulating the development of compulsions. This work hypothesized that dopamine, a critical modulator of striatal synaptic plasticity, could control alterations in corticostriatal circuits leading to the development of compulsions (defined as continued reward-seeking in the face of punishment). The first aim utilized dual-site fiber photometry to measure dopamine axon activity in the dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) as compulsions emerged. Individual variability in the speed with which compulsions emerged was predicted by DMS dopamine axon activity. In the second aim, we manipulated the activity of DMS and DLS dopamine terminals using excitatory and inhibitory optogenetics. Amplifying the DMS dopamine signal accelerated animals’ transitions to compulsion, whereas inhibition led to learning delays. In contrast, amplifying DLS dopamine signaling had no effect on the emergence of compulsions. These results establish DMS dopamine signaling as a key controller of the development of compulsive reward-seeking.
History
Advisor
Wirtshafter, Robert DLerner, Talia NChair
Wirtshafter, Robert DDepartment
PsychologyDegree Grantor
University of Illinois at ChicagoDegree Level
- Doctoral
Degree name
PhD, Doctor of PhilosophyCommittee Member
Roitman, Jamie D Ragozzino, Michael E Lasek, Amy WSubmitted date
December 2021Thesis type
application/pdfLanguage
- en