Biology Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/2749
Browse
2 results
Search Results
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 LONG-TERM IMPACT OF PREVIOUS COCAINE SELF-ADMINISTRATION ON DECISION-MAKING AND STRIATAL CIRCUITRY(2017) Burton, Amanda Claire; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Current theories of addiction suggest that impaired decision-making observed in individuals that chronically abuse drugs reflects a decrease in goal-directed behaviors and an increase in habitual behaviors governed by neural representations of response-outcome and stimulus-response associations, respectively. The striatum is a critical input component to the basal ganglia, which is a complex set of subcortical brain structures involved in the selection and execution of actions. Striatal sub-regions are some of the first brain regions to be affected by drugs of abuse, yet we still do not fully understand how decision-making and neural correlates in these regions are affected by drug exposure or disruptions within the circuit. My project was designed to study behavioral and neural changes in the striatum after previous cocaine self-administration or pharmacological lesion while rats perform a complex decision-making task. I therefore implemented a cocaine self-administration or pharmacological lesion protocol and recorded from single neurons in striatal sub-regions, specifically the nucleus accumbens core (NAc) and dorsal lateral striatum (DLS), during performance of an odor-guided decision-making task in which reward contingencies often changed. This task independently manipulated value of expected reward by changing the delay to or size of reward across a series of blocks of trials. I found that previous cocaine self-administration made rats more impulsive, biasing choice behavior toward more immediate reward. After cocaine exposure, there were fewer task-responsive neurons in the NAc and in those that remained we observed diminished directional and value encoding compared to controls. Surprisingly, in the DLS I found evidence of increased response-outcome associations and no evidence of enhanced stimulus-response associations after cocaine exposure. After disrupting communication between the NAc and DLS, I found evidence of enhanced stimulus-response associations in the DLS during task performance. This suggests that cocaine exposure impacts decision-making and neural activity in the striatum that manifests in more complex ways than simply disrupting striatal circuitry as current theories of addiction suggest.