Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
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Item CORTICAL AND STRIATAL MECHANISMS OF VALUE-BASED DECISION-MAKING AND THEIR DISRUPTION IN ADDICTION(2022) Hadfield, Heather; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)For decisions both great and small, the brain utilizes an extensive network that integrates value assessment, reward prediction, and motivation to quickly and efficiently select the most beneficial option while minimizing aversive consequences for ourselves. Numerous psychiatric conditions, in particular drug addiction, can disrupt this network and impair decision-making behavior. It is therefore important to understand the neural underpinnings of decision-making and how neural activity and its associated behavior are disrupted by drugs of abuse. My dissertation will expand on current studies of this circuitry by examining epigenetic and neurophysiological mechanisms of value-based decision-making within two regions of the brain. In my final aim, I explore a new behavioral assay that may be used to study these and other regions relevant for value-based decision-making in the context of another complex behavior.In my first aim, I have recorded from single neurons in the rat dorsal lateral striatum (DLS) after overexpressing histone deacetylase 5 (HDAC5), an epigenetic enzyme implicated in incubation of craving, in the dorsal striatum (DS). In my second aim I used pharmacological lesion and single-neuron recording combined with cocaine self-administration techniques to study anterior insula, a region well-known for combining internal and external experience but largely under-studied in the context of higher cognitive processes. These studies were conducted while rats performed an odor-guided decision-making task in which the value of rewards were manipulated by either the delay to or the size of the reward across a series of trial blocks. I have found overexpression of HDAC5 in DS promoted inflexible, faster, and automatic behavior in the decision-making task while increasing DLS’s response to reward cues- similar to previous studies examining DLS activity and behavior after cocaine self-administration. In my studies of insula, I found recording from this region novel, global signals of reward value that seemed to reflect the overall structure of the behavioral task. Following cocaine-exposure, these signals were diminished while immediate rewards were over-represented on a trial-by-trial basis, leading to steeper discounting of delayed rewards. Additional studies lesioning this region promoted faster reaction times and increased goal-directed behavior. Together, these results provide insights into how drugs of abuse may impair behavioral flexibility and the tracking of long-term changes in reward from multiple mechanisms. However, it is still unknown how these changes in value assessment give rise to complex impairments of behavior. As a first step to addressing this issue, I used a new task to examine how chronic drug use- which disrupts both neural signals in the corticostriatal circuit and epigenetic enzymes- also impairs the complex ability to delay gratification. This final study replicated well-established findings of drug-induced reversal-learning impairment, but surprisingly did not alter decision-making. This collection of work demonstrates the complexity with which drug exposure alters neural circuitry and value-based decision-making, and additionally shows the importance of utilizing complex behavioral assays to explore the relationship between brain and behavior.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.Item Response inhibition and the cortico-striatal circuit(2015) Bryden, Daniel William; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The ability to flexibly control or inhibit unwanted actions is critical for everyday behavior. Lack of this capacity is characteristic of numerous psychiatric diseases including attention deficit hyperactivity disorder (ADHD). My project is designed to study the neural underpinnings of response inhibition and to what extent these mechanisms are disrupted in animals with impaired impulse control. I therefore recorded single neurons from dorsal striatum, orbitofrontal cortex, and medial prefrontal cortex from rats performing a novel rodent variant of the classic "stop signal" task used in clinical settings. This task asks motivated rats to repeatedly produce simple actions to obtain rewards while needing to semi-occasionally inhibit an already initiated response. To take this a step further, I compared normal rats to rats prenatally exposed to nicotine in order to better understand the mechanism underlying inhibitory control. Rats exposed to nicotine before birth show abnormal attention, poor inhibitory control, and brain deficits consistent with impairments seen in humans prenatally exposed to nicotine and those with ADHD. I found that dorsal striatum neurons tend to encode the direction of a response and the motor refinement necessary to guide behaviors within the task rather than playing a causal role in response inhibition. However the orbitofrontal cortex, a direct afferent of dorsal striatum, possesses the capacity to inform the striatum of the correct action during response inhibition within the critical time window required to flexibly alter an initiated movement. On the other hand, medial prefrontal cortex functions as a conflict “monitor” to broadly increase preparedness for flexible response inhibition by aggregating current and past conflict history. Lastly, rat pups exposed to nicotine during gestation exhibit faster movement speeds and reduced capacity for inhibitory behavior. Physiologically, prenatal nicotine exposure manifests in a hypoactive prefrontal cortex, diminished encoding of task parameters, and reduced capacity to maintain conflict information.