Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item SEX DIFFERENCES IN THE FOREBRAIN DOPAMINERGIC CIRCUIT(2022) Manion, Matthew Timothy Coon; Glasper, Erica R; Wang, Kuan Hong; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Several psychiatric disorders exhibit different incidence rates in men and women and areassociated with dysfunctions in forebrain dopaminergic circuits. Although anatomical and functional sex differences in the brain have been studied, little is known about sex differences in the forebrain dopaminergic circuits associated with behavioral dysfunction. We hypothesized that known sex differences in forebrain dopamine circuit-associated behaviors would be the result of sex differences in forebrain dopamine circuit anatomy. As a first step to address this hypothesis, we combined a mouse transgenic driver line (tyrosine hydroxylase promoter-driven Cre recombinase) with virally encoded fluorescent reporters (FLEX-tdTomato and SynaptophysinGFP) to compare the density of midbrain dopaminergic axon projections and terminal boutons in dopamine projection target regions. Using this technique, we analyzed projections from the ventral tegmental area (VTA) to prefrontal cortex and basolateral amygdala (BLA) in male and female adult mice. Multiple analyses at 10x and 25x magnification revealed higher bouton density in BLA in males compared to females. To determine if this anatomical difference is mediated by gonadal steroid hormones, subjects were treated with a drug used to reduce gonadal steroid hormone production in clinical populations, leuprolide acetate (Lupron), before anatomical measures. Leuprolide administration resulted in a reduction in circulating testosterone, but did not show an effect on dopamine circuit anatomy. The finding of an anatomical sex difference in the forebrain dopamine circuit provides a structural foundation for further investigation of how sex differences in brain circuits may underlie behavioral dysfunction that play roles in psychiatric illnesses.Item THE ROLE OF THE VENTRAL STRIATUM AND AMYGDALA IN REINFORCEMENT LEARNING(2021) Taswell, Craig Anthony; Butts , Daniel; Averbeck , Bruno; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Adaptive behavior requires that organisms choose wisely to gain rewards and avoid punishment. Reinforcement learning refers to the behavioral process of learning about the value of choices, based on previous choice outcomes. From an algorithmic point of view, rewards and punishments exist on opposite sides of a single value axis. However, simple distinctions between rewards and punishments and their theoretical expression on a single value axis hide considerable psychological complexities that underlie appetitive and aversive reinforcement learning. A broad set of neural circuits, including the amygdala and frontal-striatal systems, have been implicated in mediating learning from gains and losses. The ventral striatum (VS) and amygdala have been implicated in several aspects of this process. To examine the role of the VS and amygdala in learning from gains and losses, we compared the performance of macaque monkeys with VS lesions, with amygdala lesions, and un-operated controls on a series of reinforcement learning tasks. In these tasks monkeys gained or lost tokens, which were periodically cashed out for juice, as outcomes for choices. We found that monkeys with VS lesions had a deficit in learning to choose between cues that differed in reward magnitude. Monkeys with VS lesions performed as well as controls when choices involved a potential loss. In contrast, we found that monkeys with amygdala lesions performed as well as controls across all conditions. Further analysis revealed that the deficits we found in monkeys with VS lesions resulted from a reduction in motivation, rather than the monkeys’ inability to learn the stimulus-outcome contingency.