Neurobiological mechanisms of conflict resolution and goal-directed behaviour

Abstract

This thesis investigated theories regarding the neurobiological substrates of conflict resolution in rodents. An operant biconditional discrimination task was used that modelled elements of response conflict similar to that observed in the human Stroop task. Correct performance required the use of incidental (context) cues to guide performance during compound cues that signalled conflicting responses. This task was used to test hypotheses related to the role of dopamine, the frontal cortex and hippocampus in conflict resolution. In addition, a transgenic mouse model of frontotemporal dementia (tau V337M) was used to assess the effects of this mutation on frontal cortex-dependent conflict resolution. The first set of experiments examined the effects of dopaminergic agonists (d- amphetamine and phencyclidine) on conflict resolution in rats. It was found that the modulation of dopamine tone generally disrupted conditional responding as opposed to selectively disrupting conflict resolution. In order to understand how genetic models of human frontal cortex disorders influence conflict resolution, the conflict task was successfully adapted for use with mice. Lesions of the prefrontal cortex in mice selectively disrupted the use of context cues to resolve response conflict. Hippocampal lesions, however, did not disrupt contextual control of response conflict. In contrast to predictions, mice with the tau V337M mutation linked to frontotemporal dementia were not impaired at conflict resolution. However, these mice were impaired in acquisition of a spatial navigation task, indicative of abnormal hippocampal function. In summary, this thesis provides evidence that rats and mice are able to use incidental contextual cues to influence responding during situations in which punctate cues signal conflicting responses. Modulation of dopamine did not influence response conflict in this paradigm. Nevertheless, conflict resolution was reliant upon an intact frontal cortex (but not hippocampus) in rodents. Surprisingly, a mouse genetic model of frontotemporal dementia did not impair conflict resolution but did impair elements of the associative structures supporting performance