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Title: The role of cortico-striato-thalamo-cortical circuits of the brain in inter-temporal choice and its underlying behavioural mechanisms in the rat
Author: Bezzina, Gilbert
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Inter-temporal choice refers to a situation where a decision has to be made between two or more rewards of different sizes that are available after different delays. There is evidence that abnormalities of inter-temporal choice behaviour (biased selection of smaller immediate rewards in preference to larger delayed rewards) may be associated with some clinical conditions, such as attention deficit hyperactivity disorder (ADHD), which are characterised by deficient impulse control. Evidence suggests that abnormal inter-temporal choice behaviour and occurrence of ADHD may develop from dysfunction of cortico-striato-thalamo-cortical (CSTC) circuits in the brain. Three experiments described in this thesis examined. the effects of a systematic disruption of CSTC circuits on inter-temporal choice performance in rats. The results of these experiments generated hypotheses about the roles of some components of the CSTC circuits in regulating the efficacy or 'instantaneous valueof reinforcers, which were tested in two further experiments that employed quantitative analyses of performance on a single-operandum progressive ratio (PR) schedule of reinforcement. Chapter 1 reviews the literature dealing with key theoretical concepts and experimental findings pertaining to inter-temporal choice and single-operandum schedules. Section 1. J is a preamble that offers a general background to the work that was carried out as well as the aims and brief outline of the experiments that were conducted. Section 1.2 reviews the history of the concept of inter-temporal choice and the way it has been accounted for from economic as well as behavioural perspectives. It examines the empirical data from the experimental analysis of behaviour in inter-temporal choice tasks and gives an account of the putative neurobiology that underlies this behaviour. Section 1.3 reviews the theoretical as well as practical notions of the use of PR schedules and their potential for dissociating behavioural mechanisms involved in inter-temporal choice behaviour. Chapters 2~ describe a series of five experiments that examined the effects on inter-temporal choice and PR performance following damage inflicted to the CSTC circuits in the rat brain. Experiment I sought to elaborate on previous findings that lesions of the core of the nucleus accumbens (Acbe) promote preference for smaller earlier reinforcers over larger delayed reinforcers in inter-temporal choice paradigms by clarifying whether this reflects an effect of the lesion on the rate of delay discounting, on sensitivity to reinforcer magnitude, or both. A quantitative method that allows effects on delay discounting to be distinguished from effects on sensitivity to reinforcer size showed that lesions to the Acbe promote preference for smaller, earlier reinforcers, and suggested that this reflects an effect of the lesion on the rate of delay discounting. Experiment II examined the effect of disconnecting the orbital prefrontal cortex (OPFC) from the Ache on inter-temporal choice performance. Rats were given excitotoxin-induced contralateral lesions of the OPFC and Acbe (disconnection), severing of the anterior corpus callosum (callosotomy), a combined lesion (disconnection+ca11osotomy) or sham lesions. Using the same behavioural training and quantitative method as in Experiment L the disconnection+callosotomy group showed a lower intercept of the indifference function than the sham-lesioned group; the disconnection group showed a similar but less robust effect, whereas tbe callosotomy group did not differ significantly from the sbam-lesioned group. The results suggest that OPFC-AcbC connections are involved in delay discounting of food reinforcers. Tbe subthalamic nucleus (STN) is a major relay in the indirect striatofugal pathway and plays an important role in extrapyramidal motor control. Recent findings indicate that it may also play a role in modulating the efficacy of food reinforcers. The objective of Experiment ill was to examine the effect of lesions of the STN on inter-temporal choice performance. Following bilateral excitotoxin-induced or sham lesions of the STN and behavioural training and methodology as Experiments I and IT, STN-lesioned rats showed a flatter slope of the indifference function (implying higher instantaneous reinforcer values) compared to sham-lesioned rats; there was no difference in intercepts between the two groups. The results agree with recent findings that indicate a function of the STN in incentive value. However, in contrast to some previous studies, these results do not indicate a role of the STN in delay discounting. Experiment N investigated the effect of AcbC lesions on performance on a PR schedule using a quantitative model that discriminates between effects of interventions on motor and motivational processes. Following bilateral excitotoxin-induced and sham lesions of the AcbC, rats were trained to respond for food reinforcers under a PR schedule. The motor parameter, d, was significantly higher in the AcbC-Iesioned than the sham-Iesioned group, reflecting lower overall response rates in the lesioned group. The motivational parameter, a, was sensitive to changes in reinforcer magnitude, but showed no significant difference between the two groups. The AcbC-lesioned group showed longer post-reinforcement pauses and lower running response rates than the sham-lesioned group. The results suggest that destruction of the Ache impairs response capacity but does not alter the efficacy of food reinforcers. The results are consistent with the findings in Experiment I that Ache lesions do not alter sensitivity to reinforcer size in inter-temporal choice schedules. The objective of Experiment V was to examine the effect of lesions of the STN on performance on a PR schedule using the same quantitative model as in Experiment IV. After bilateral excitotoxin-induced and sham lesions of the STN, rats were given the same behavioural training under the same protocol as in Experiment N . Parameter t5 was significantly higher in the STN-lesioned than the sham-lesioned group. indicating lower overall response rates in the lesioned group. Parameter a was significantly higher in the STN-lesioned group than in the sham-Iesioned group, consistent with the results from Experiment ill which suggested enhanced instantaneous reinforcer value in the STN-lesioned group compared to the sham-lesioned group. The results suggest that destruction of the STN impairs response capacity and enhances the incentive value of food reinforcers. In conclusion, chapter 7 recapitulates the findings from all the experiments that were carried out and discusses the emerging implications about the role of CSIC circuits in regulating inter-temporal choice behaviour, and the behavioural processes that may underline this role.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available