Considerable evidence suggests that a number of neurodegenerative disorders, particularly those that affect cortico-basal ganglia circuits, such as Huntingtons, Parkinsons, Alzheimers disease, obsessive-compulsive disorder and so on, have in common a range of deficits in planning and other executive functions associated with goal-directed action. Over the last decade or so we have been studying these deficits using a rodent model of goal-directed action, derived from manipulations of the instrumental conditioning paradigm, together with a battery of behavioral tests. Generally, human actions are sensitive to both the causal relation between the action and the goal as well as the current value of the goal. Likewise, rats can be trained to acquire new actions to gain access to rewarding events, e.g. learning to press a lever for sugar, and their tendency to select and initiate these responses is sensitive to changes in both the contingent relation between the action and outcome delivery and the current reward or incentive value of that outcome. Furthermore, just as in humans, choice of action is heavily influenced by extraneous information (advertising being the prime example), in rats a stimulus associated with a specific instrumental outcome can strongly alter the probability of performing actions associated with that outcome. This renewal application requests continued support for our investigation of the neural bases of instrumental conditioning focusing particularly on the neural systems that mediate (i) the representation of rewarding events and the effect that these events have on the performance of goal-directed actions; and (ii) the interaction of Pavlovian and instrumental conditioning through an assessment of the neural mechanisms that mediate the influence of cues that predict reward on the selection and initiation of instrumental actions. ? ? Considerable evidence suggests that a number of neurodegenerative disorders, particularly those that affect cortico-basal ganglia circuits such as Huntingtons, Parkinsons Alzheimers disease obsessive-compulsive disorder and so on, have in common a range of deficits in planning and other executive functions associated with goal-directed action. As these disorders make clear, the ability to acquire and exert control over specific actions is highly adaptive, allowing us and other animals to control the environment in the service of our basic needs and desires. Nevertheless, although research into the physiological systems that subserve learning processes generally has been of ongoing concern, the neural basis of goal- directed action remains poorly understood. The broad, long term objective of the current project is, therefore, to understand the neural mechanisms that control the learning and performance of goal directed or instrumental actions. Over the last decade striking advances have been achieved in our understanding of the behavioral determinants of instrumental conditioning in animals. Specifically, instrumental performance has been found to reflect the integration of (i) representations of the relations between an action and its consequences; with (ii) representations of the incentive value of those consequences. Powerful behavioral procedures will be used to focus on the role of cortico-striato-limbic interactions in processes involved in representing the reward value of the instrumental outcome and in the sensitivity of instrumental performance to reward-related cues. ? ? ? ?
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