Biology
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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.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.