An investigation of the role of cortico-striato-thalamo-cortical circuits in the regulation of inter-temporal choice behaviour in rats. (360G-Wellcome-077727_Z_05_Z)

Inter-temporal choice is choice between rewards that differ in their sizes and delays. It is believed that an abnormality of inter-temporal choice (predeliction for 'impulsive choice') may contribute to the behavioural disturbance seen in some clinical conditions. It is suggested that this abnormality of inter-temporal choice may arise from dysfunction of cortico-striato-thalamo-cortical (CSTC) circuits. To date there have been no systematic investigations of the effects of manipulating CSTC function on inter-temporal choice in animals. The project will use behavioural methodology based on a mathematical theory of inter-temporal choice developed by the applicants. A series of experiments will examine the effects of disrupting the function of three putative CSTC circuits (designated by their cortical components, as orbital prefrontal, ventromedial prefrontal and dorsomedial prefrontal) on performance on inter-temporal choice schedules. The effects of lesions of the cortical component of the circuits will be examined, followed by examination of the effects of disconnecting the cortical component from its striatal target, and selective dopamine depletion in these regions. Hypotheses will be derived from these experiments about effects of the lesions on processes believed to underlie inter-temporal choice (delay-discounting, sensitivity to reinforcer size). These hypotheses will be addressed using quantitative single-operandum operant schedules.